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Polyadenylation [poly(A)] signals (PAS) are a defining feature of eukaryotic protein-coding genes. The central sequence motif AAUAAA was identified in the mid-1970s and subsequently shown to require flanking, auxiliary elements for both 3'-end cleavage and polyadenylation of premessenger RNA (pre-mRNA) as well as to promote downstream transcriptional(More)
The requirement of poly(A) signals to elicit transcription termination of RNA polymerase II (pol II) is firmly established. However, little else is known about the actual process of pol II transcription termination. Evidence presented in this paper, based on analysis of nascent transcripts of the human beta- and epsilon-globin genes, demonstrates that pol(More)
The messenger RNA processing reactions of capping, splicing, and polyadenylation occur cotranscriptionally. They not only influence one another's efficiency and specificity, but are also coordinated by transcription. The phosphorylated CTD of RNA polymerase II provides key molecular contacts with these mRNA processing reactions throughout transcriptional(More)
The pathway from gene activation in the nucleus to mRNA translation and decay at specific locations in the cytoplasm is both streamlined and highly interconnected. This review discusses how pre-mRNA processing, including 5' cap addition, splicing, and polyadenylation, contributes to both the efficiency and fidelity of gene expression. The connections of(More)
microRNAs (miRNAs) are generated from long primary (pri-) RNA polymerase II (Pol II)-derived transcripts by two RNase III processing reactions: Drosha cleavage of nuclear pri-miRNAs and Dicer cleavage of cytoplasmic pre-miRNAs. Here we show that Drosha cleavage occurs during transcription acting on both independently transcribed and intron-encoded miRNAs.(More)
We have identified novel nuclear transcripts in the human beta-globin locus using nuclear run-on analysis in erythroid cell lines and in situ hybridization analysis of erythroid tissue. These transcripts extend across the LCR and intergenic regions but are undetectable in nonerythroid cells. Surprisingly, transient transfection of a beta-globin gene(More)
Analysis of nascent transcription from the human epsilon- and beta-globin genes shows that transcriptional termination occurs within 1.5 kb of the poly(A) site and is dependent on the presence of functional poly(A) signals. Even so, transcripts that have not been cleaved at the poly(A) site are detected up to the termination region, suggesting that there is(More)
The sequence A-A-U-A-A-A is present in six different purified messenger RNA molecules (specifically the alpha-and beta-globulin mRNAs of rabbit and human, the immunoglobulin light chain mRNA of mouse (MOPC 21) and the ovalbumin mRNA of chicken) about 20 residues away from the 3'-terminal poly (A) sequence. In addition, a large selection of the 3' non-coding(More)
Inducible genes in yeast retain a "memory" of recent transcriptional activity during periods of short-term repression, allowing them to be reactivated faster when reinduced. This confers a rapid and versatile gene expression response to the environment. We demonstrate that this memory mechanism is associated with gene loop interactions between the promoter(More)
Reconstruction of a gene with its introns removed results in reduced levels of cytoplasmic mRNA. This is partly explained by introns promoting the export of mRNA through coupling splicing to nuclear export processes. However, we show here that splicing signals can have a direct role in enhancing gene transcription. Removal of promoter proximal splice(More)