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Dynamic phosphorylation of the RNA polymerase II CTD repeats (YS 2 PTS 5 PS 7) is coupled to transcription and may act as a " code " that controls mRNA synthesis and processing. To examine the "code" in budding yeast, we mapped genome-wide CTD S2, 5 and 7 phosphorylations (PO4) and compared them with the CTD-associated termination factors, Nrd1 and Pcf11.(More)
The universal pre-mRNA processing events of 5' end capping, splicing, and 3' end formation by cleavage/polyadenylation occur co-transcriptionally. As a result, the substrate for mRNA processing factors is a nascent RNA chain that is being extruded from the RNA polymerase II exit channel at 10-30 bases per second. How do processing factors find their(More)
Promoter and enhancer elements can influence alternative splicing, but the basis for this phenomenon is not well understood. Here we investigated how different transcriptional activators affect the decision between inclusion and exclusion (skipping) of the fibronectin EDI exon. A mutant of the acidic VP16 activation domain called SW6 that preferentially(More)
Promoter-proximal pausing by RNA polymerase II (Pol II) ensures gene-specific regulation and RNA quality control. Structural considerations suggested a requirement for initiation-factor eviction in elongation-factor engagement and pausing of transcription complexes. Here we show that selective inhibition of Cdk7--part of TFIIH--increases TFIIE retention,(More)
DNA damage induces apoptosis and many apoptotic genes are regulated via alternative splicing (AS), but little is known about the control mechanisms. Here we show that ultraviolet irradiation (UV) affects cotranscriptional AS in a p53-independent way, through the hyperphosphorylation of RNA polymerase II carboxy-terminal domain (CTD) and a subsequent(More)
The origins of our current understanding of control of transcription elongation lie in pioneering experiments that mapped RNA polymerase II on viral and cellular genes. These studies first uncovered the surprising excess of polymerase molecules that we now know to be situated at the at the 5' ends of most genes in multicellular organisms. The pileup of pol(More)
The Saccharomyces cerevisiae mRNA export adaptor Yra1 binds the Pcf11 subunit of cleavage-polyadenylation factor CF1A that links export to 3' end formation. We found that an unexpected consequence of this interaction is that Yra1 influences cleavage-polyadenylation. Yra1 competes with the CF1A subunit Clp1 for binding to Pcf11, and excess Yra1 inhibits 3'(More)
The C-terminal domain (CTD) of the large subunit of RNA polymerase II (Pol II) influences many steps in the synthesis of an mRNA and helps control the final destiny of the mature transcript. ADAR2 edits RNA by converting adenosine to inosine within double-stranded or structured RNA. Site-selective A-to-I editing often occurs at sites near exon/intron(More)
We investigated whether a continuous transcript is necessary for co-transcriptional pre-mRNA processing. Cutting an intron with the fast-cleaving hepatitis delta ribozyme, but not the slower hammerhead, inhibited splicing. Therefore, exon tethering to RNA polymerase II (Pol II) cannot rescue splicing of a transcript severed by a ribozyme that cleaves(More)