Document Detail


Promoter-proximal polyadenylation sites reduce transcription activity.
MedLine Citation:
PMID:  23028143     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites on transcription requires promoter proximity, as demonstrated using artificial constructs and supported by a genome-wide data set. Importantly, transcription down-regulation can be recapitulated in a gene context devoid of splice sites by placing a functional bona fide pA site/transcription terminator within ~500 base pairs of the promoter. In contrast, promoter-proximal positioning of a pA site-independent histone gene terminator supports high transcription levels. We propose that optimal communication between a pA site-dependent gene terminator and its promoter critically depends on gene length and that short RNA polymerase II-transcribed genes use specialized termination mechanisms to maintain high transcription levels.
Authors:
Pia K Andersen; Søren Lykke-Andersen; Torben Heick Jensen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes & development     Volume:  26     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2012-12-05     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2169-79     Citation Subset:  IM    
Affiliation:
Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Down-Regulation
Gene Expression Regulation*
HIV-1 / metabolism
Humans
Point Mutation / genetics
Polyadenylation / genetics*
Promoter Regions, Genetic / genetics*
RNA 3' End Processing / genetics
Ribonucleoprotein, U1 Small Nuclear / genetics
Chemical
Reg. No./Substance:
0/Ribonucleoprotein, U1 Small Nuclear
Comments/Corrections

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