Flowering time is controlled by precision in gene regulation mediated by different pathways. Two Arabidopsis thaliana components of the autonomous flowering pathway, FCA and FPA, function as genetically independent trans -acting regulators of alternative cleavage and polyadenylation. FCA and FPA directly associate with chromatin at the locus encoding the floral repressor FLC, but appear to control FLC transcription by mediating alternative polyadenylation of embedded non-coding antisense RNAs. These findings prompt the re-examination of how other factors control FLC expression, as it is formally possible that they function primarily to control alternative processing of antisense RNAs. As co-expressed sense and antisense gene pairs are widespread in eukaryotes, alternative processing of antisense RNAs may represent a significant form of gene regulation.

How RNA-binding proteins recognize their complement of targets in a complex cellular environment remains poorly understood. Sequence degeneracy and redundancy of short motifs at genomic scales have mostly eluded predictions of specific target genes for gene-specific ELAV (embryonic lethal abnormal visual system)/Hu proteins that bind ubiquitous AU-rich motifs. Using the genetic tools of Drosophila , we have analysed binding properties of ELAV in vitro and ELAV-dependent regulation of its major target ewg ( erect wing ) in neurons. These studies reveal that an integral part of ELAV gene-specific regulation involves combinatorial binding to variably spaced short U-rich motifs on an extensive binding site.

ELAV (embryonic lethal abnormal visual system)/Hu family proteins are prototype RNA-binding proteins with binding preferences for AU-rich regions. Due to frequent occurrence of AU-rich motifs in introns and untranslated regions, it is poorly understood how gene-specific RNA-binding proteins, such as ELAV/Hu family members, recognize their complement of target RNAs in a complex cellular environment. The powerful genetic tools of Drosophila make the fruitfly an excellent model to study alternative mRNA processing in vivo in a developing organism. Recent sequencing of 12 Drosophila genomes will provide a novel resource to enhance our understanding of how gene-specific regulation of mRNA processing is achieved by ELAV/Hu family proteins.

We are developing a computational pipeline to use surveys of Affymetrix GeneChips as a discovery tool for unravelling some of the biology associated with post-transcriptional processing of RNA. This work involves the integration of a number of bioinformatics resources, from comparing annotations to processing images to determining the structure of transcripts. The rapidly growing datasets of GeneChips available to the community puts us in a strong position to discover novel biology about post-transcriptional processing, and should enable us to determine the mechanisms by which some groups of genes make co-ordinated changes in their production of isoforms.

Overexpression of the enzyme COX-2 (cyclo-oxygenase-2) is associated with various pathophysiological conditions, including inflammatory diseases and different cancers. Increased synthesis of COX-2 in fetal membranes and the myometrium is also linked with the onset of term and preterm labour. COX - 2 gene regulation is controlled at various levels including gene transcription and post-transcriptional events. The present article focuses on the complexity of COX - 2 gene regulation and reviews current concepts that highlight: (i) transcription of COX - 2 is induced rapidly and transiently in response to a plethora of stimuli; (ii) COX - 2 mRNA stability and translational efficiency is governed by multiple regulatory elements within the 3′-untranslated region; (iii) specific microRNAs and RNA-binding proteins influence COX - 2 mRNA stability; and (iv) regulation of COX-2 involves alternative polyadenylation.

Plants control their flowering time in order to ensure that they reproduce under favourable conditions. The components involved in this complex process have been identified using a molecular genetic approach in Arabidopsis and classified into genetically separable pathways. The autonomous pathway controls the level of mRNA encoding a floral repressor, FLC , and comprises three RNA-binding proteins, FCA, FPA and FLK. FCA interacts with the 3′-end RNA-processing factor FY to autoregulate its own expression post-transcriptionally and to control FLC . Other components of the autonomous pathway, FVE and FLD, regulate FLC epigenetically. This combination of epigenetic and post-transcriptional control gives precision to the control of FLC expression and flowering time.