The regulation of translation has emerged as a major determinant of gene expression and is critical for both normal cellular function and the development of disease. Numerous studies have highlighted the diverse, and sometimes related, mechanisms which underlie the regulation of global translation rates and the translational control of specific mRNAs. In the present paper, we discuss the emerging roles of the basal translation factor PABP [poly(A)-binding protein] in mRNA-specific translational control in metazoa which suggest that PABP function is more complex than first recognized.

Introduction

Cytoplasmic PABPs [poly(A)-binding proteins] are conserved throughout eukaryotes and act as central determinants of mRNA translation and stability by binding to the poly(A) tail of mRNAs (reviewed in [1,2]). Perturbation of PABP function leads to a variety of phenotypes in invertebrates [35], including lethality, highlighting the importance of their function. In vertebrates, the biological consequences associated with loss or perturbation of PABP function remains to be determined, but the presence of multiple PABPs with a similar domain organization [PABP1, PABP4, ePABP (embryonic PABP) and the mammalian-specific tPABP (testis-specific PABP); Figure 1A] has lead to the supposition that their functions may be redundant. However, to date, most work has focused on the prototypical family member, PABP1, with little information being available for the other PABPs.

PABPs and the cap-dependent pathway

Figure 1
PABPs and the cap-dependent pathway

(A) The domain structure of the human PABP family is depicted identifying the regions of PABP1 which interact with the protein partners discussed in the text. Although DAZL is depicted, all DAZ family members interact with the C-terminal region. The binding site for eIF4B is not clearly defined, but requires the C-terminus. RRMs 1 and 2 mediate the majority of poly(A)-binding, but the RNA-binding specificity of RRMs 3 and 4 remains unclear, although affinity towards AU-rich sequences has been shown. The percentage identity of each domain in other family members to PABP1 is given. PABP4 and ePABP may be represented by multiple transcripts and predicted transcripts PABPC4–002 and PABPC1L-201 were utilized. In most cases, PABP1 partner proteins have not been demonstrated to interact with the other family members. (B) Simplified overview of cap-dependent translation initiation. (1) The small ribosomal subunit and associated eIFs (43S) are recruited to the 5′ end of the mRNA by the action of the eIF4F complex (see the text for details). (2) The 43S complex then scans the 5′-UTR to locate an initiation codon. (3) Following initiation codon recognition, initiation factor release and joining of the large (60S) ribosomal subunit leads to formation of a translationally competent 80S ribosome. PABP1 interactions with the scaffold protein eIF4G (4G), the eIF4G-like protein PAIP1 and the eIF4A (4A) co-factor eIF4B (4B) are thought to be important for PABP-mediated stimulation of initiation. eRF3–PABP interactions may increase the pool of available ribosomal subunits. ORF, open reading frame. The 5′-cap is depicted as a solid black spot and the poly(A) tail as AAAAAA. For clarity, not all eIFs or interactions are depicted.

Figure 1
PABPs and the cap-dependent pathway

(A) The domain structure of the human PABP family is depicted identifying the regions of PABP1 which interact with the protein partners discussed in the text. Although DAZL is depicted, all DAZ family members interact with the C-terminal region. The binding site for eIF4B is not clearly defined, but requires the C-terminus. RRMs 1 and 2 mediate the majority of poly(A)-binding, but the RNA-binding specificity of RRMs 3 and 4 remains unclear, although affinity towards AU-rich sequences has been shown. The percentage identity of each domain in other family members to PABP1 is given. PABP4 and ePABP may be represented by multiple transcripts and predicted transcripts PABPC4–002 and PABPC1L-201 were utilized. In most cases, PABP1 partner proteins have not been demonstrated to interact with the other family members. (B) Simplified overview of cap-dependent translation initiation. (1) The small ribosomal subunit and associated eIFs (43S) are recruited to the 5′ end of the mRNA by the action of the eIF4F complex (see the text for details). (2) The 43S complex then scans the 5′-UTR to locate an initiation codon. (3) Following initiation codon recognition, initiation factor release and joining of the large (60S) ribosomal subunit leads to formation of a translationally competent 80S ribosome. PABP1 interactions with the scaffold protein eIF4G (4G), the eIF4G-like protein PAIP1 and the eIF4A (4A) co-factor eIF4B (4B) are thought to be important for PABP-mediated stimulation of initiation. eRF3–PABP interactions may increase the pool of available ribosomal subunits. ORF, open reading frame. The 5′-cap is depicted as a solid black spot and the poly(A) tail as AAAAAA. For clarity, not all eIFs or interactions are depicted.

PABP1 (also referred to as PABPC1) has four non-identical RRMs (RNA-recognition motifs) that are not functionally equivalent and a C-terminal region that consists of a variable protein-rich linker region and the highly conserved PABC domain [6] (Figure 1A). Whereas the RRMs mediate both RNA and protein interactions, the C-terminal region interacts only with proteins, although its role in PABP1–PABP1 interactions enhances co-operative poly(A) binding [7] (Figure 1A). When bound to the poly(A) tail, PABP1 acts as a primary determinant of translation efficiency by facilitating initiation. Initiation (reviewed in detail in [8]) starts with the binding of the eIF (eukaryotic initiation factor) 4F complex, composed of eIF4E, eIF4G and eIF4A, to the cap at the 5′-end of the mRNA (Figure 1B; for an animation of initiation, see http://www.biochemj.org/bj/426/0001/bj4260001add.htm [9]). This interaction is primarily mediated by the cap-binding factor eIF4E. The cap complex facilitates the removal of secondary structure within the 5′-UTR (untranslated region), by the helicase action of eIF4A, and recruitment of the small ribosomal subunit and associated factors (eIF2–GTP–Met, eIF3, eIF1, eIF1A and eIF5), through the interaction between eIF4G and eIF3. The small ribosomal subunit subsequently scans the 5′-UTR until initiation codon recognition triggers release of initiation factors and large ribosomal subunit joining. The effects of PABP1 on metazoan initiation appear to be pleiotropic, stimulating both large and small ribosomal subunit recruitment, although our knowledge of its function is far from complete (reviewed in detail in [1,2]). Several translation initiation factors, including eIF4G, PAIP (PABP-interacting protein) 1 and eIF4B [1,2,10], have been suggested to contribute to the action of PABP (Figure 1). Of these, most attention has focused on the PABP1–eIF4G interaction which effectively circularizes mRNAs in an ‘end-to-end’ complex (Figure 1B) due to the simultaneous interaction of eIF4G with PABP1 and eIF4E. This complex stabilizes the association of eIF4F with the cap [1113], resulting in enhanced small subunit joining. End-to-end complexes are thought to be further stabilized by the PABP1–PAIP1 interaction [14]. The role of the interaction of PABP1 with eIF4B, a factor that stimulates the helicase action of eIF4A, remains to be addressed. Interestingly, an interaction with the translation termination factor, eRF3 (eukaryotic release factor 3), may also contribute to initiation by increasing the pool of ribosomal subunits available for reloading [15].

Whereas the effects of poly(A) tail-bound PABP1 on initiation are essentially ubiquitous, other features of mRNAs, such as the presence of secondary structure in the 5′-UTR, can affect the extent of PABP1-dependence of individual mRNAs [16]. In addition, PABP1 has mRNA-specific roles in translational regulation which are mediated by the presence of defined regulatory elements within these mRNAs. In the present paper, we discuss the diversity of these emerging PABP1-regulatory mechanisms.

Changes in poly(A) tail length regulate the translation of many mRNAs

mRNAs generally exit the nucleus with a poly(A) tail of defined length (approx. 250 adenosines), which is gradually shortened until mRNA turnover is initiated. However, dynamic changes in poly(A) tail length can also regulate the translation of specific mRNAs. Such changes were originally characterized in germ cells and early embryos, where many maternal mRNAs are deadenylated as they emerge from the nucleus and then stored in a translationally silent, but stable, state until they are activated (reviewed in [17,18]). Activation of these mRNAs is often accompanied by an increase in poly(A) tail length which, in some well-studied cases, is demonstrated to be required for translational activation (reviewed in [17]). The newly synthesized poly(A) tails act as a platform to recruit PABPs [19], with each PABP covering 20–25 adenosines [1,2], thereby driving translational activation. Although the role of PABPs in activating these mRNAs is akin to their normal global role in promoting translation from the poly(A) tail, polyadenylation in the cytoplasm requires specific 3′-UTR elements [20,21], which were found to be present in approx. 30–45% of mRNAs analysed [20]. In addition to promoting the translation of these mRNAs, PABPs may also participate in the control of their poly(A) tail length by protecting the newly synthesized tails from deadenylation [22]. Interestingly, cytoplasmic polyadenylation has also been shown to occur in somatic cells such as neurons [23], indicating that the role of PABPs in this specialized form of regulation is likely to extend to other biological processes.

PABPs as poly(A)-tail-independent activators of mRNA-specific translation

The ability of PABPs to stimulate translation when artificially tethered to sites within the 3′-UTR of reporter mRNAs [19,24] suggested that PABPs may be able to promote translation when recruited by elements other than the poly(A) tail. Recent observations suggest that they fulfil this role in biological contexts where poly(A) tails are often short or even absent.

The DAZ (deleted in azoospermia) family of RNA-binding proteins activate the translation of a subset of mRNAs in germ cells by binding to 3′-UTR regulatory elements (reviewed in [25]) (Figure 2A). Both PABP1 and ePABP, the predominant PABP in oocytes, interact directly with DAZ family members in an RNA-independent manner [26]. Mapping of the domains that mediate the DAZ family translational activator function revealed that the PABP interaction was required for stimulation in vivo [26]. Location of the DAZ-binding site in the C-terminal region of PABPs suggests a model for their function in promoting initiation, as a simultaneous interaction with eIF4G and/or PAIP1 could occur allowing the formation of end-to-end complexes in a manner analogous to that of the poly(A) tail [26] (Figure 2A). In this regard, it is interesting that at least one verified in vivo target mRNA of DAZL (DAZ-like) is stored with a poly(A) tail of only approx. 20 nucleotides [27,28]. Furthermore, as DAZ family proteins are capable of activating the translation of unadenylated reporter mRNAs, recruitment of PABPs via protein–protein interactions is sufficient to mediate poly(A)-independent effects on initiation [26].

Positive regulation of specific mRNAs by PABP1 independent of its poly(A)-tail-mediated functions

Figure 2
Positive regulation of specific mRNAs by PABP1 independent of its poly(A)-tail-mediated functions

(A) Recruitment of PABPs to mRNAs via protein–protein interactions with DAZ family members (DAZ, BOULE and DAZL, which is depicted) can stimulate initiation independently of the poly(A) tail. The spatial arrangement of respective binding sites makes it likely that simultaneous PABP1 interactions with DAZL and eIF4G (4G) or PAIP1 can be maintained, but it is less clear whether eIF4B (4B) interaction can occur (dotted arrow). AAA depicts a short poly(A) tail. (B) PABP1 can stimulate translation of mRNAs by binding internal poly(A)-rich regions within the 3′-UTR, presumably utilizing the same initiation factor partners as PABP1 bound to the poly(A) tail. (C) YB-1 translationally represses its own mRNA. At high concentrations, PABP1 binds to an overlapping site in the YB-1 3′-UTR, causing eviction of YB-1 and relief of translational repression. PABP1 bound to the poly(A) tail of YB-1 mRNA (AAAAAA) is not depicted for clarity. In (AC), the spatial organization of the depicted eIFs is to facilitate the illustration of PABP1 interactions. ORF, open reading frame. The 5′-cap is depicted as a solid black spot.

Figure 2
Positive regulation of specific mRNAs by PABP1 independent of its poly(A)-tail-mediated functions

(A) Recruitment of PABPs to mRNAs via protein–protein interactions with DAZ family members (DAZ, BOULE and DAZL, which is depicted) can stimulate initiation independently of the poly(A) tail. The spatial arrangement of respective binding sites makes it likely that simultaneous PABP1 interactions with DAZL and eIF4G (4G) or PAIP1 can be maintained, but it is less clear whether eIF4B (4B) interaction can occur (dotted arrow). AAA depicts a short poly(A) tail. (B) PABP1 can stimulate translation of mRNAs by binding internal poly(A)-rich regions within the 3′-UTR, presumably utilizing the same initiation factor partners as PABP1 bound to the poly(A) tail. (C) YB-1 translationally represses its own mRNA. At high concentrations, PABP1 binds to an overlapping site in the YB-1 3′-UTR, causing eviction of YB-1 and relief of translational repression. PABP1 bound to the poly(A) tail of YB-1 mRNA (AAAAAA) is not depicted for clarity. In (AC), the spatial organization of the depicted eIFs is to facilitate the illustration of PABP1 interactions. ORF, open reading frame. The 5′-cap is depicted as a solid black spot.

Although PABP1 is targeted during infection by a wide variety of viruses to achieve host cell shut-off (reviewed in [9]), a role in activating DV (dengue virus) translation has also been reported. DV has a positive-sense RNA genome with a capped 5′-UTR and a non-adenylated 3′-UTR. In the absence of a poly(A) tail, the 3′-UTR of DV appears to promote translation [2931] with a 3′-SL (stem–loop) near the terminus of the 3′-UTR accounting for approx. 50% of the translational stimulation [30]. Viral factors do not appear to be required for this function [30,32] and, consistent with this, a number of cellular factors including PABP1 have been shown to bind the 3′-UTR [3335]. Purified PABP1 binds to two apparently single-stranded regions containing runs of adenosines upstream of the 3′-SL (Figure 2B) [35]. The functionality of this interaction was tested in cell-free extracts using reporter mRNAs bearing the DV 5′- and 3′-UTRs, showing that their translation was sensitive to the presence of the PABP1 inhibitor PAIP2 [35], which interferes with PABP1–poly(A) and PABP1–eIF4G interactions [10]. Although the importance of PABP1, relative to other factors which bind the 3′-SL, in stimulating DV translation in infected cells remains to be determined, this observation suggests that the DV RNA may recruit PABP1 via an internal 3′-UTR-binding site to promote end-to-end complex formation (Figure 2B).

The role of PABPs in mRNA-specific translational repression

PABP1 has been shown to mediate translational repression of its own mRNA both in vitro and in cell lines, by binding to an approx. 60-nt element containing multiple short (six to eight) adenosine tracts within its 5′-UTR [36,37]. The affinity of PABP1 for these 5′-UTR sites appears to be lower than that for the poly(A) tail [38], such that these ARSs (autoregulatory sites) are only occupied when PABP1 levels are high. The ARS is conserved from yeast to humans, and PABP1 autoregulation is likely to be responsible for observations that overexpression of PABP1 is frequently unsuccessful in vivo (e.g. [3]). PABP1 autoregulates its own translation as part of a heterotrimeric ARC (autoregulatory complex) with IMP-1 (insulin-like growth factor II mRNA-binding protein-1) and Unr (upstream of N-ras), which are suggested to increase the affinity of PABP1 for the regulatory element [38]. Since the ARS sequences are located in a cap-distal position within the 5′-UTR, this increase in RNA-binding affinity may be necessary to allow the autoregulatory complex to effectively block the scanning of ribosomal subunits through the 5′-UTR [39] (Figure 3A). Intriguingly, mammalian PABP4 appears to have an element resembling the ARS, raising the possibility that these two PABPs may be subject to co-ordinate regulation by PABP1. It remains to be established whether other PABPs also interact with Unr or IMP-1 to mediate regulation of PABP1 levels in cells where multiple PABPs are present.

PABP1 function in the negative regulation of specific mRNAs

Figure 3
PABP1 function in the negative regulation of specific mRNAs

(A) PABP1 binds to the 5′-UTR of its own mRNA as part of an autoregulatory complex with Unr and IMP-1. Located distal to the cap, the complex apparently inhibits translation by blocking scanning of the 43S complex. (B) Argonaute (Ago) bound to miRNA (white line) interacts with GW182. PABP1 acts as a co-activator of the miRNA silencing complex. GW182 is thought to compete with eIF4G and/or poly(A) for PABP1 binding (red lines). PABP1 is also thought to be important for the recruitment of the CAF1–CCR4–Not1 deadenylase complex. (C) Translational repression of msl-2 mRNA by Sxl bound at the 3′-UTR is dependent on Unr and PABP1. Repression affects 43S complex recruitment by an unknown mechanism that does not affect the PABP1–eIF4G (4G) interaction. ORF, open reading frame. The 5′-cap is depicted as a solid black spot and the poly(A) tail as AAAAAA.

Figure 3
PABP1 function in the negative regulation of specific mRNAs

(A) PABP1 binds to the 5′-UTR of its own mRNA as part of an autoregulatory complex with Unr and IMP-1. Located distal to the cap, the complex apparently inhibits translation by blocking scanning of the 43S complex. (B) Argonaute (Ago) bound to miRNA (white line) interacts with GW182. PABP1 acts as a co-activator of the miRNA silencing complex. GW182 is thought to compete with eIF4G and/or poly(A) for PABP1 binding (red lines). PABP1 is also thought to be important for the recruitment of the CAF1–CCR4–Not1 deadenylase complex. (C) Translational repression of msl-2 mRNA by Sxl bound at the 3′-UTR is dependent on Unr and PABP1. Repression affects 43S complex recruitment by an unknown mechanism that does not affect the PABP1–eIF4G (4G) interaction. ORF, open reading frame. The 5′-cap is depicted as a solid black spot and the poly(A) tail as AAAAAA.

Recently, a novel activity of PABP1 in miRNA (microRNA)-mediated silencing has been shown to occur through its association with the miRISC (miRNA-induced silencing complex) (Figure 3B). PABP1 is recruited by miRISC component GW182 [40,41], which also interacts with Argonaute, and is considered to be the effector of miRNA-mediated silencing. The GW182-binding site has been reported to be in the RRM region of Drosophila PABP [40], but in the C-terminal region of mammalian PABP1 [41] (Figure 1A). This may reflect an ability of GW182 to interact with multiple regions of PABP, reminiscent of other PABP-interacting proteins, such as PAIP1 and PAIP2 [10]. Based in large part on the position of the GW182 interaction site, two different models for PABP action in miRNA-mediated silencing have been proposed. The first posits that GW182 binding to PABP causes translational repression as a result of reduced eIF4G interactions with the RRMs [40]. The second favours a model in which deadenylation is promoted either by a PAIP2-like effect of GW182 in reducing PABP/poly(A) binding or by enhancing the activity of the CAF1 (CCR4-associated factor 1)–CCR4–Not1 deadenylase complex [41]. However, these activities may not be mutually exclusive, with both modes of regulation probably contributing to silencing (Figure 3B).

Other roles of PABP in mRNA-specific repression

PABP1 appears to be present in complexes with mRNA-specific RNA-binding proteins that mediate translational repression. In Drosophila, Sxl (sex-lethal) regulates the splicing and translation of mRNAs such as msl-2 (male-specific lethal 2) which is involved in dosage compensation [42]. Sxl binds both the 3′-UTR and 5′-UTR of this mRNA and analysis of initiation intermediates showed that these interactions block both small ribosomal subunit joining and scanning respectively, ensuring effective repression of msl-2 [43]. 3′-UTR-mediated repression of small ribosomal subunit joining, but not the scanning block, also requires Unr which interacts with both Sxl and PABP1 [44,45] (Figure 3C). This repressor complex does not appear to disrupt the PABP1–eIF4G interaction or the ability of eIF4G to bind the 5′-UTR [46]. Therefore it is unclear whether another aspect of eIF4G function, e.g. its ability to interact with eIF3, or another PABP1 interaction, e.g. PAIP1 or eRF3, is affected. However, it is possible that PABP1 may act as a cofactor of Sxl/Unr rather than a target of repression. Thus PABP1- and Unr-containing complexes mediate mRNA-specific repression from both the 5′-UTR and the 3′-UTR, albeit through different mechanisms and partners, raising the possibility that additional regulatory events may utilize this interaction.

The general RNA-binding protein YB-1 (Y-box 1) has been suggested to render translation more PABP1-dependent, at least in vitro, by inhibiting the binding of eIF4G to the RNA adjacent to the cap [47,48], thereby destabilizing the eIF4F–cap interaction [49]. Interestingly, PABP1 also appears to participate in the regulation of YB-1 protein levels. Binding of YB-1 to sequences in the 3′-UTR of its own mRNA inhibits an early step in initiation, resulting in autoregulation [50,51]. PABP1 can bind an overlapping site in the YB-1 3′-UTR consisting of multiple short (3–4 nt) adenosine stretches, displacing YB-1 protein and relieving repression of YB-1 translation (Figure 2C) [51]. It is suggested that this feedback mechanism contributes to the control of overall cellular translation rates, as the antagonistic action of YB-1 and PABP1 will be affected by their respective levels.

Perspectives

To date, relatively few examples of mRNA-specific regulation by PABP1 have been identified. The mechanisms by which regulation is achieved remain, for the most part, poorly defined and their delineation will require a complete understanding of how PABP1 stimulates initiation. However, the diversity of mechanisms identified raises the possibility that mRNA-specific regulation by PABP1 represents a widespread strategy of translational control. The interaction of PABP1 with a growing number of protein partners, which mediate its roles in global and mRNA-specific translation as well as mRNA turnover, raises several questions: how many of these interactions can PABP1 participate in at any given time, how dynamic are these interactions and how is its participation in different regulatory complexes regulated? Moreover, in most cases, it is unclear to what extent other PABPs share the protein interactions described in the present paper. Nonetheless, it is tempting to speculate that mRNAspecific roles may, in some cases, be mediated through PABP-specific interactions, suggesting that the multiple PABPs in vertebrates may have partially distinct functions. Unravelling the growing complexity of post-transcriptional control by the PABP family promises to be both challenging and rewarding.

Post-Transcriptional Control: mRNA Translation, Localization and Turnover: A Biochemical Society Focused Meeting held at University of Edinburgh, U.K., 8–10 June 2010. Organized and Edited by Matthew Brook (Edinburgh, U.K.), Mark Coldwell (Southampton, U.K.), Simon Morley (Sussex, U.K.) and Nicola Gray (Edinburgh, U.K.).

Abbreviations

     
  • ARS

    autoregulatory site

  •  
  • CAF1

    CCR4-associated factor 1

  •  
  • DAZ

    deleted in azoospermia

  •  
  • DAZL

    DAZ-like

  •  
  • DV

    dengue virus

  •  
  • eIF

    eukaryotic initiation factor

  •  
  • eRF3

    eukaryotic release factor 3

  •  
  • IMP-1

    insulin-like growth factor II mRNA-binding protein-1

  •  
  • miRNA

    microRNA

  •  
  • msl-2

    male-specific lethal 2

  •  
  • PABP

    poly(A)-binding protein

  •  
  • ePABP

    embryonic PABP

  •  
  • PAIP

    PABP-interacting protein

  •  
  • RRM

    RNA-recognition motif

  •  
  • SL

    stem–loop

  •  
  • Sxl

    sex-lethal

  •  
  • Unr

    upstream of N-ras

  •  
  • UTR

    untranslated region

  •  
  • YB-1

    Y-box 1

We thank Ted Pinner and Richard Smith for preparation of the Figures and members of the laboratory for discussions and constructive criticism pertaining to the present review.

Funding

Work in the laboratory is funded by Medical Research Council (MRC) core funding, an MRC Senior Non-Clinical Fellowship and Wellcome Trust projects grants to N.K.G.

References

References
1
Mangus
D.A.
Evans
M.C.
Jacobson
A.
Poly(A)-binding proteins: multifunctional scaffolds for the post-transcriptional control of gene expression
Genome Biol.
2003
, vol. 
4
 pg. 
223
 
2
Gorgoni
B.
Gray
N.K.
The roles of cytoplasmic poly(A)-binding proteins in regulating gene expression: a developmental perspective
Brief. Funct. Genomics Proteomics
2004
, vol. 
3
 (pg. 
125
-
141
)
3
Sigrist
S.J.
Thiel
P.R.
Reiff
D.F.
Lachance
P.E.
Lasko
P.
Schuster
C.M.
Postsynaptic translation affects the efficacy and morphology of neuromuscular junctions
Nature
2000
, vol. 
405
 (pg. 
1062
-
1065
)
4
Ciosk
R.
DePalma
M.
Priess
J.R.
ATX-2, the C. elegans ortholog of ataxin 2, functions in translational regulation in the germline
Development
2004
, vol. 
131
 (pg. 
4831
-
4841
)
5
Maciejowski
J.
Ahn
J.H.
Cipriani
P.G.
Killian
D.J.
Chaudhary
A.L.
Lee
J.I.
Voutev
R.
Johnsen
R.C.
Baillie
D.L.
Gunsalus
K.C.
, et al. 
Autosomal genes of autosomal/X-linked duplicated gene pairs and germ-line proliferation in Caenorhabditis elegans
Genetics
2005
, vol. 
169
 (pg. 
1997
-
2011
)
6
Kozlov
G.
Trempe
J.
Khaleghpour
K.
Kahvejian
A.
Ekiel
I.
Gehring
K.
Structure and function of the C-terminal PABC domain of human poly(A)-binding protein
Proc. Natl. Acad. Sci. U.S.A.
2001
, vol. 
98
 (pg. 
4409
-
4413
)
7
Kuhn
U.
Wahle
E.
Structure and function of poly(A) binding proteins
Biochim. Biophys. Acta
2004
, vol. 
1678
 (pg. 
67
-
84
)
8
Jackson
R.J.
Hellen
C.U.
Pestova
T.V.
The mechanism of eukaryotic translation initiation and principles of its regulation
Nat. Rev. Mol. Cell Biol.
2010
, vol. 
11
 (pg. 
113
-
127
)
9
Smith
R.W.
Gray
N.K.
Poly(A)-binding protein (PABP): a common viral target
Biochem. J.
2010
, vol. 
426
 (pg. 
1
-
12
)
10
Derry
M.C.
Yanagiya
A.
Martineau
Y.
Sonenberg
N.
Regulation of poly(A)-binding protein through PABP-interacting proteins
Cold Spring Harbor Symp. Quant. Biol.
2006
, vol. 
71
 (pg. 
537
-
543
)
11
Kahvejian
A.
Svitkin
Y.V.
Sukarieh
R.
M'Boutchou
M.N.
Sonenberg
N.
Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms
Genes Dev.
2005
, vol. 
19
 (pg. 
104
-
113
)
12
Borman
A.M.
Michel
Y.M.
Kean
K.M.
Biochemical characterisation of cap-poly(A) synergy in rabbit reticulocyte lysates: the eIF4G–PABP interaction increases the functional affinity of eIF4E for the capped mRNA 5′-end
Nucleic Acids Res.
2000
, vol. 
28
 (pg. 
4068
-
4075
)
13
von Der Haar
T.
Ball
P.D.
McCarthy
J.E.
Stabilization of eukaryotic initiation factor 4E binding to the mRNA 5′-cap by domains of eIF4G
J. Biol. Chem.
2000
, vol. 
275
 (pg. 
30551
-
30555
)
14
Martineau
Y.
Derry
M.C.
Wang
X.
Yanagiya
A.
Berlanga
J.J.
Shyu
A.B.
Imataka
H.
Gehring
K.
Sonenberg
N.
The poly(A)-binding protein-interacting protein 1 binds to eIF3 to stimulate translation
Mol. Cell. Biol.
2008
, vol. 
28
 (pg. 
6658
-
6667
)
15
Uchida
N.
Hoshino
S.
Imataka
H.
Sonenberg
N.
Katada
T.
A novel role of the mammalian GSPT/eRF3 associating with poly(A)binding protein in cap/poly(A)-dependent translation
J. Biol. Chem.
2002
, vol. 
277
 (pg. 
50286
-
50292
)
16
Gallie
D.R.
Ling
J.
Niepel
M.
Morley
S.J.
Pain
V.M.
The role of 5′-leader length, secondary structure and PABP concentration on cap and poly(A) tail function during translation in Xenopus oocytes
Nucleic Acids Res.
2000
, vol. 
28
 (pg. 
2943
-
2953
)
17
Gray
N.K.
Wickens
M.
Control of translation initiation in animals
Annu. Rev. Cell Dev. Biol.
1998
, vol. 
14
 (pg. 
399
-
458
)
18
Richter
J.D.
Hershey
J.W.B.
Mathews
M.B.
Sonenberg
N
Dynamics of poly(A) addition and removal during development
Translational Control
1996
Cold Spring Harbor
Cold Spring Harbor Laboratory Press
(pg. 
481
-
503
)
19
Gray
N.K.
Coller
J.M.
Dickson
K.S.
Wickens
M.
Multiple portions of poly(A)-binding protein stimulate translation in vivo
EMBO J.
2000
, vol. 
19
 (pg. 
4723
-
4733
)
20
Pique
M.
Lopez
J.M.
Foissac
S.
Guigo
R.
Mendez
R.
A combinatorial code for CPE-mediated translational control
Cell
2008
, vol. 
132
 (pg. 
434
-
448
)
21
Arumugam
K.
Wang
Y.
Hardy
L.L.
MacNicol
M.C.
MacNicol
A.M.
Enforcing temporal control of maternal mRNA translation during oocyte cell-cycle progression
EMBO J.
2010
, vol. 
29
 (pg. 
387
-
397
)
22
Kim
J.H.
Richter
J.D.
RINGO/cdk1 and CPEB mediate poly(A) tail stabilization and translational regulation by ePAB
Genes Dev.
2007
, vol. 
21
 (pg. 
2571
-
2579
)
23
Richter
J.D.
CPEB: a life in translation
Trends Biochem. Sci.
2007
, vol. 
32
 (pg. 
279
-
285
)
24
Wilkie
G.S.
Gautier
P.
Lawson
D.
Gray
N.K.
Embryonic poly(A)-binding protein stimulates translation in germ cells
Mol. Cell. Biol.
2005
, vol. 
25
 (pg. 
2060
-
2071
)
25
Brook
M.
Smith
J.W.
Gray
N.K.
The DAZL and PABP families: RNA-binding proteins with interrelated roles in translational control in oocytes
Reproduction
2009
, vol. 
137
 (pg. 
595
-
617
)
26
Collier
B.
Gorgoni
B.
Loveridge
C.
Cooke
H.J.
Gray
N.K.
The DAZL family proteins are PABP-binding proteins that regulate translation in germ cells
EMBO J.
2005
, vol. 
24
 (pg. 
2656
-
2666
)
27
Tay
J.
Richter
J.D.
Germ cell differentiation and synaptonemal complex formation are disrupted in CPEB knockout mice
Dev. Cell
2001
, vol. 
1
 (pg. 
201
-
213
)
28
Reynolds
N.
Collier
B.
Bingham
V.
Gray
N.K.
Cooke
H.J.
Translation of the synaptonemal complex component Sycp3 is enhanced in vivo by the germ cell specific regulator Dazl
RNA
2007
, vol. 
13
 (pg. 
974
-
981
)
29
Edgil
D.
Diamond
M.S.
Holden
K.L.
Paranjape
S.M.
Harris
E.
Translation efficiency determines differences in cellular infection among dengue virus type 2 strains
Virology
2003
, vol. 
317
 (pg. 
275
-
290
)
30
Holden
K.L.
Harris
E.
Enhancement of dengue virus translation: role of the 3′ untranslated region and the terminal 3′ stem–loop domain
Virology
2004
, vol. 
329
 (pg. 
119
-
133
)
31
Holden
K.L.
Stein
D.A.
Pierson
T.C.
Ahmed
A.A.
Clyde
K.
Iversen
P.L.
Harris
E.
Inhibition of dengue virus translation and RNA synthesis by a morpholino oligomer targeted to the top of the terminal 3′ stem–loop structure
Virology
2006
, vol. 
344
 (pg. 
439
-
452
)
32
Chiu
W.W.
Kinney
R.M.
Dreher
T.W.
Control of translation by the 5′- and 3′-terminal regions of the dengue virus genome
J. Virol.
2005
, vol. 
79
 (pg. 
8303
-
8315
)
33
De Nova-Ocampo
M.
Villegas-Sepulveda
N.
del Angel
R.M.
Translation elongation factor-1α, La, and PTB interact with the 3′ untranslated region of dengue 4 virus RNA
Virology
2002
, vol. 
295
 (pg. 
337
-
347
)
34
Paranjape
S.M.
Harris
E.
Y box-binding protein-1 binds to the dengue virus 3′-untranslated region and mediates antiviral effects
J. Biol. Chem.
2007
, vol. 
282
 (pg. 
30497
-
30508
)
35
Polacek
C.
Friebe
P.
Harris
E.
Poly(A)-binding protein binds to the non-polyadenylated 3′ untranslated region of dengue virus and modulates translation efficiency
J. Gen. Virol.
2009
, vol. 
90
 (pg. 
687
-
692
)
36
de Melo Neto
O.P.
Standart
N.
Martins de Sa
C.
Autoregulation of poly(A)-binding protein synthesis in vitro
Nucleic Acids Res.
1995
, vol. 
23
 (pg. 
2198
-
2205
)
37
Wu
J.
Bag
J.
Negative control of the poly(A)-binding protein mRNA translation is mediated by the adenine-rich region of its 5′-untranslated region
J. Biol. Chem.
1998
, vol. 
273
 (pg. 
34535
-
34542
)
38
Patel
G.P.
Ma
S.
Bag
J.
The autoregulatory translational control element of poly(A)-binding protein mRNA forms a heteromeric ribonucleoprotein complex
Nucleic Acids Res.
2005
, vol. 
33
 (pg. 
7074
-
7089
)
39
Bag
J.
Feedback inhibition of poly(A)-binding protein mRNA translation: a possible mechanism of translation arrest by stalled 40 S ribosomal subunits
J. Biol. Chem.
2001
, vol. 
276
 (pg. 
47352
-
47360
)
40
Zekri
L.
Huntzinger
E.
Heimstadt
S.
Izaurralde
E.
The silencing domain of GW182 interacts with PABPC1 to promote translational repression and degradation of microRNA targets and is required for target release
Mol. Cell. Biol.
2009
, vol. 
29
 (pg. 
6220
-
6231
)
41
Fabian
M.R.
Mathonnet
G.
Sundermeier
T.
Mathys
H.
Zipprich
J.T.
Svitkin
Y.V.
Rivas
F.
Jinek
M.
Wohlschlegel
J.
Doudna
J.A.
, et al. 
Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-dependent deadenylation
Mol. Cell
2009
, vol. 
35
 (pg. 
868
-
880
)
42
Penalva
L.O.
Sanchez
L.
RNA binding protein sex-lethal (Sxl) and control of Drosophila sex determination and dosage compensation
Microbiol. Mol. Biol. Rev.
2003
, vol. 
67
 (pg. 
343
-
359
)
43
Beckmann
K.
Grskovic
M.
Gebauer
F.
Hentze
M.W.
A dual inhibitory mechanism restricts msl-2 mRNA translation for dosage compensation in Drosophila
Cell
2005
, vol. 
122
 (pg. 
529
-
540
)
44
Duncan
K.
Grskovic
M.
Strein
C.
Beckmann
K.
Niggeweg
R.
Abaza
I.
Gebauer
F.
Wilm
M.
Hentze
M.W.
Sex-lethal imparts a sex-specific function to UNR by recruiting it to the msl-2 mRNA 3′ UTR: translational repression for dosage compensation
Genes Dev.
2006
, vol. 
20
 (pg. 
368
-
379
)
45
Abaza
I.
Coll
O.
Patalano
S.
Gebauer
F.
Drosophila UNR is required for translational repression of male-specific lethal 2 mRNA during regulation of X-chromosome dosage compensation
Genes Dev.
2006
, vol. 
20
 (pg. 
380
-
389
)
46
Duncan
K.E.
Strein
C.
Hentze
M.W.
The SXL–UNR corepressor complex uses a PABP-mediated mechanism to inhibit ribosome recruitment to msl-2 mRNA
Mol. Cell
2009
, vol. 
36
 (pg. 
571
-
582
)
47
Nekrasov
M.P.
Ivshina
M.P.
Chernov
K.G.
Kovrigina
E.A.
Evdokimova
V.M.
Thomas
A.A.
Hershey
J.W.
Ovchinnikov
L.P.
The mRNA-binding protein YB-1 (p50) prevents association of the eukaryotic initiation factor eIF4G with mRNA and inhibits protein synthesis at the initiation stage
J. Biol. Chem.
2003
, vol. 
278
 (pg. 
13936
-
13943
)
48
Svitkin
Y.V.
Evdokimova
V.M.
Brasey
A.
Pestova
T.V.
Fantus
D.
Yanagiya
A.
Imataka
H.
Skabkin
M.A.
Ovchinnikov
L.P.
Merrick
W.C.
Sonenberg
N.
General RNA-binding proteins have a function in poly(A)-binding protein-dependent translation
EMBO J.
2009
, vol. 
28
 (pg. 
58
-
68
)
49
Yanagiya
A.
Svitkin
Y.V.
Shibata
S.
Mikami
S.
Imataka
H.
Sonenberg
N.
Requirement of RNA binding of mammalian eukaryotic translation initiation factor 4GI (eIF4GI) for efficient interaction of eIF4E with the mRNA cap
Mol. Cell. Biol.
2009
, vol. 
29
 (pg. 
1661
-
1669
)
50
Skabkina
O.V.
Skabkin
M.A.
Popova
N.V.
Lyabin
D.N.
Penalva
L.O.
Ovchinnikov
L.P.
Poly(A)-binding protein positively affects YB-1 mRNA translation through specific interaction with YB-1 mRNA
J. Biol. Chem.
2003
, vol. 
278
 (pg. 
18191
-
18198
)
51
Skabkina
O.V.
Lyabin
D.N.
Skabkin
M.A.
Ovchinnikov
L.P.
YB-1 autoregulates translation of its own mRNA at or prior to the step of 40S ribosomal subunit joining
Mol. Cell. Biol.
2005
, vol. 
25
 (pg. 
3317
-
3323
)