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J. Biol. Chem., Vol. 283, Issue 12, 7949-7961, March 21, 2008

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Identification of the Cellular Targets of the Transcription Factor TCERG1 Reveals a Prevalent Role in mRNA Processing^*

James L. Pearson, Timothy J. Robinson^¶||1, Manuel J. Muñoz^**, Alberto R. Kornblihtt^**, and Mariano A. Garcia-Blanco²

From the Department of Molecular Genetics and Microbiology, ^¶Department of Molecular Cancer Biology, ^||Medical Scientist Training Program, Department of Medicine, Center for RNA Biology, Duke University Medical Center, Durham, North Carolina 27710 and ^**Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, (C1428EHA) Buenos Aires, Argentina

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.

Received for publication, November 15, 2007 , and in revised form, January 9, 2008.

^* This work was supported in part by National Institutes of Health Grant 1RO1 GM071037 (to M. A. G. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Tables 1-6.

¹ Supported by the Medical Scientist Training Program at Duke University.

² To whom correspondence should be addressed. Tel.: 919-613-8636; Fax: 919-613-8646; E-mail: garci001{at}mc.duke.edu.

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