Document Detail


Identification of the cellular targets of the transcription factor TCERG1 reveals a prevalent role in mRNA processing.
MedLine Citation:
PMID:  18187414     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The transcription factor TCERG1 (also known as CA150) associates with RNA polymerase II holoenzyme and alters the elongation efficiency of reporter transcripts. TCERG1 is also found as a component of highly purified spliceosomes and has been implicated in splicing. To elucidate the function of TCERG1, we used short interfering RNA-mediated knockdown followed by en masse gene expression analysis to identify its cellular targets. Analysis of data from HEK293 and HeLa cells identified high confidence targets of TCERG1. We found that targets of TCERG1 were enriched in microRNA-binding sites, suggesting the possibility of post-transcriptional regulation. Consistently, reverse transcription-PCR analysis revealed that many of the changes observed upon TCERG1 knockdown were because of differences in alternative mRNA processing of the 3'-untranslated regions. Furthermore, a novel computational approach, which can identify alternatively processed events from conventional microarray data, showed that TCERG1 led to widespread alterations in mRNA processing. These findings provide the strongest support to date for a role of TCERG1 in mRNA processing and are consistent with proposals that TCERG1 couples transcription and processing.
Authors:
James L Pearson; Timothy J Robinson; Manuel J Muñoz; Alberto R Kornblihtt; Mariano A Garcia-Blanco
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-01-10
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-03-17     Completed Date:  2008-05-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7949-61     Citation Subset:  IM    
Affiliation:
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Gene Expression Profiling
Humans
MicroRNAs / genetics,  metabolism
Oligonucleotide Array Sequence Analysis
RNA Splicing / physiology*
RNA, Messenger / genetics,  metabolism*
RNA, Small Interfering / genetics
Reverse Transcriptase Polymerase Chain Reaction
Spliceosomes / genetics,  metabolism*
Trans-Activators / antagonists & inhibitors,  genetics,  metabolism*
Transcription, Genetic / physiology*
Grant Support
ID/Acronym/Agency:
1R01 GM071037/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/MicroRNAs; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/TCERG1 protein, human; 0/Trans-Activators

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