We report that a DBHS (Drosophila behaviour, human splicing) family protein, p54nrb, binds both BRG1 (Brahma-related gene 1) and Brm (Brahma), catalytic subunits of the SWI/SNF (switch/sucrose non-fermentable) chromatin remodelling complex, and also another core subunit of this complex, BAF60a. The N-terminal region of p54nrb is sufficient to pull-down other core subunits of the SWI/SNF complex, suggesting that p54nrb binds SWI/SNF-like complexes. PSF (polypyrimidine tract-binding protein-associated splicing factor), another DBHS family protein known to directly bind p54nrb, was also found to associate with the SWI/SNF-like complex. When sh (short hairpin) RNAs targeting Brm were retrovirally expressed in a BRG1-deficient human cell line (NCI-H1299), the resulting clones showed down-regulation of the TERT (telomerase reverse transcriptase) gene and an enhancement of ratios of exon-7-and-8-excluded TERT mRNA that encodes a β-site-deleted inactive protein. All of these clones display growth arrest within 2 months of the Brm-knockdown. In NCI-H1299 cells, Brm, p54nrb, PSF and RNA polymerase II phosphorylated on CTD (C-terminal domain) Ser2 specifically co-localize at a region incorporating an alternative splicing acceptor site of TERT exon 7. These findings suggest that, at the TERT gene locus in human tumour cells containing a functional SWI/SNF complex, Brm, and possibly BRG1, in concert with p54nrb, would initiate efficient transcription and could be involved in the subsequent splicing of TERT transcripts by accelerating exon-inclusion, which partly contributes to the maintenance of active telomerase.
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Research Article|
March 13 2008
Brm transactivates the telomerase reverse transcriptase (TERT) gene and modulates the splicing patterns of its transcripts in concert with p54nrb
Taiji Ito;
Taiji Ito
*Division of Host–Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
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Hirotaka Watanabe;
Hirotaka Watanabe
*Division of Host–Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
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Nobutake Yamamichi;
Nobutake Yamamichi
*Division of Host–Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
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Shunsuke Kondo;
Shunsuke Kondo
*Division of Host–Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
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Toshio Tando;
Toshio Tando
*Division of Host–Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
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Takeshi Haraguchi;
Takeshi Haraguchi
*Division of Host–Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
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Taketoshi Mizutani;
Taketoshi Mizutani
*Division of Host–Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
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Kouhei Sakurai;
Kouhei Sakurai
*Division of Host–Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
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Shuji Fujita;
Shuji Fujita
*Division of Host–Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
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Tomonori Izumi;
Tomonori Izumi
†Division of Proteomics Research, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
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Toshiaki Isobe;
Toshiaki Isobe
†Division of Proteomics Research, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
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Hideo Iba
Hideo Iba
1
*Division of Host–Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
1To whom correspondence should be addressed (email iba@ims.u-tokyo.ac.jp)
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Publisher: Portland Press Ltd
Received:
August 08 2007
Revision Received:
October 24 2007
Accepted:
November 28 2007
Accepted Manuscript online:
November 28 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 411 (1): 201–209.
Article history
Received:
August 08 2007
Revision Received:
October 24 2007
Accepted:
November 28 2007
Accepted Manuscript online:
November 28 2007
Citation
Taiji Ito, Hirotaka Watanabe, Nobutake Yamamichi, Shunsuke Kondo, Toshio Tando, Takeshi Haraguchi, Taketoshi Mizutani, Kouhei Sakurai, Shuji Fujita, Tomonori Izumi, Toshiaki Isobe, Hideo Iba; Brm transactivates the telomerase reverse transcriptase (TERT) gene and modulates the splicing patterns of its transcripts in concert with p54nrb. Biochem J 1 April 2008; 411 (1): 201–209. doi: https://doi.org/10.1042/BJ20071075
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