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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)
Phosphorylation of the RNA polymerase (Pol) II C-terminal domain (CTD) repeats (1-YSPTSPS-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 Ser2, Ser5 and Ser7 phosphorylations and the CTD-associated termination factors Nrd1 and Pcf11.(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)
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)
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)
NAD(P)H:quinone oxidoreductase 1 (NQO1) is implicated in both chemoprevention and bioactivation of DNA-damaging antitumor agents. NQO1 is mainly cytosolic, but distribution in other cellular compartments, particularly in tumor cells, is poorly defined. Nuclear NQO1 in HT29 human colon carcinoma and H661 human non-small cell lung cancer cells was observed(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 report that under 'transcriptional stress' in budding yeast, when most pol II activity is acutely inhibited, rapid deposition of nucleosomes occurs within genes, particularly at 3' positions. Whereas histone H3K4 trimethylation normally marks 5' ends of highly transcribed genes, under 'transcriptional stress' induced by 6-azauracil (6-AU) and(More)