Document Detail


The DEAD-box protein Dhh1 promotes decapping by slowing ribosome movement.
MedLine Citation:
PMID:  22719226     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Translational control and messenger RNA (mRNA) decay represent important control points in the regulation of gene expression. In yeast, the major pathway for mRNA decay is initiated by deadenylation followed by decapping and 5'-3' exonucleolytic digestion of the mRNA. Proteins that activate decapping, such as the DEAD-box RNA helicase Dhh1, have been postulated to function by limiting translation initiation, thereby promoting a ribosome-free mRNA that is targeted for decapping. In contrast to this model, we show here that Dhh1 represses translation in vivo at a step subsequent to initiation. First, we establish that Dhh1 represses translation independent of initiation factors eIF4E and eIF3b. Second, we show association of Dhh1 on an mRNA leads to the accumulation of ribosomes on the transcript. Third, we demonstrate that endogenous Dhh1 accompanies slowly translocating polyribosomes. Lastly, Dhh1 activates decapping in response to impaired ribosome elongation. Together, these findings suggest that changes in ribosome transit rate represent a key event in the decapping and turnover of mRNA.
Authors:
Thomas Sweet; Carrie Kovalak; Jeff Coller
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-06-12
Journal Detail:
Title:  PLoS biology     Volume:  10     ISSN:  1545-7885     ISO Abbreviation:  PLoS Biol.     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-21     Completed Date:  2012-10-12     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  101183755     Medline TA:  PLoS Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1001342     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
DEAD-box RNA Helicases / genetics,  metabolism*
Eukaryotic Initiation Factor-3 / genetics,  metabolism
Eukaryotic Initiation Factor-4E / genetics,  metabolism
Protein Biosynthesis
RNA Caps / metabolism
RNA Stability / genetics,  physiology
RNA, Messenger / metabolism
Ribosomes / metabolism*
Saccharomyces cerevisiae / enzymology,  metabolism
Saccharomyces cerevisiae Proteins / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
GM080465/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Eukaryotic Initiation Factor-3; 0/Eukaryotic Initiation Factor-4E; 0/RNA Caps; 0/RNA, Messenger; 0/Saccharomyces cerevisiae Proteins; EC 3.6.1.-/DHH1 protein, S cerevisiae; EC 3.6.4.13/DEAD-box RNA Helicases
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