Identification of the cellular targets of the transcription factor TCERG1 reveals a prevalent role in mrna processing

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 TCERG...

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Detalhes bibliográficos
Autores: Pearson, J.L., Robinson, T.J., Muñoz, M.J., Kornblihtt, A.R., Garcia-Blanco, M.A.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2008
País:Argentina
Recursos:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
Repositorio:Biblioteca Digital (UBA-FCEN)
Idioma:inglés
OAI Identifier:paperaa:paper_00219258_v283_n12_p7949_Pearson
Acesso em linha:http://hdl.handle.net/20.500.12110/paper_00219258_v283_n12_p7949_Pearson
Access Level:acceso abierto
Palavra-chave:Binding energy
Binding sites
Biochemistry
Gene expression
Nucleic acids
Polymers
Proteins
RNA
Targets
Transcription factors
Analysis of datums
Cellular targets
Computational approaches
Gene expression analysis
Hela cells
High confidences
Microarray datums
Pcr analysis
Reverse transcriptions
Rna polymerase ii
Short interfering rnas
Spliceosomes
Transcriptional regulations
Untranslated regions
Transcription
messenger RNA
microRNA
small interfering RNA
transcription factor
transcription factor tcerg1
unclassified drug
TCERG1 protein, human
transactivator protein
3' untranslated region
article
binding site
cell strain HEK293
controlled study
embryo
female
gene expression
HeLa cell
human
human cell
knockout gene
microarray analysis
nucleotide sequence
priority journal
protein function
reverse transcription polymerase chain reaction
RNA processing
target cell
transcription regulation
unindexed sequence
cell line
DNA microarray
drug antagonism
gene expression profiling
genetic transcription
genetics
metabolism
physiology
RNA splicing
spliceosome
Cell Line
Gene Expression Profiling
Humans
MicroRNAs
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
RNA Splicing
RNA, Messenger
RNA, Small Interfering
Trans-Activators
Transcription, Genetic
Descrição
Resumo: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. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.