On the importance of being co-transcriptional

Abstract

Intense research in recent years has shown that many pre-mRNA processing events are co-transcriptional or at least begin during RNA synthesis by RNA polymerase II (Pol II). But is it important that pre-mRNA processing occurs co-transcriptionally? Whereas Pol II directs 5′ capping of mRNA by binding to and recruiting all three capping activities to transcription units,co-transcriptional splicing is not obligatory. In some cases, such as alternative splicing, splicing may occur post-transcriptionally owing to the slower kinetics of splicing unfavorable introns. Despite recent models in which splicing factors are bound directly to the C-terminal domain (CTD) of Pol II, little evidence supports that view. Instead, interactions between snRNPs and transcription elongation factors provide the strongest molecular evidence for a physical link between transcription and splicing. Transcription termination depends on polyadenylation signals, but, like splicing,polyadenylation per se probably begins co-transcriptionally and continues post-transcriptionally. Nascent RNA plays an important role in determining which transcripts are polyadenylated and which alternative terminal exon is used. A recent addition to co-transcriptional RNA processing is a possible RNA surveillance step prior to release of the mRNP from the transcription unit,which appears to coordinate nuclear transport with mRNA processing and may be mediated by components of the nuclear exosome.

Self-splicing of a group I intron reveals partitioning of native and misfolded RNA populations in yeast

“…This is consistent with the abundant evidence for physical and functional links between transcription and RNA splicing, polyadenylation, decay, processing, and nuclear export (Neugebauer 2002;Bentley 2005). For ribozymes and certain regulatory RNAs, the order in which RNA sequences are transcribed and the rate of elongation can determine the type of folding intermediates that are formed (e.g., Poot et al 1997;Pan et al 1999b;Diegelman-Parente and Bevilacqua 2002;Heilman-Miller and Woodson 2003;Granneman and Baserga 2005;Mahen et al 2005;Wickiser et al 2005).…”

Retinoid‐dependent mRNA expression and poly‐(A) contents in bovine oocytes meiotically arrested and/or matured in vitro

“…With the exception of editing, each of these processes have been shown to be co-transcriptional, at least some of the time (see Neugebaeuer, 2002, for a review). In animal cells, the majority of mRNAs have a 3 0 poly-(A) tail.…”

The human PAF complex coordinates transcription with events downstream of RNA synthesis

“…Cotranscriptional RNA processing events such as 5Ј-end capping, splicing, and polyadenylation are relatively well documented (for reviews, see Maniatis and Reed 2002;Neugebauer 2002;Orphanides and Reinberg 2002). In recent years, evidence for cotranscriptional RNA surveillance, particularly in higher eukaryotes, emerged as well.…”