The tumor suppressor Cdc73 functionally associates with CPSF and CstF 3′ mRNA processing factors

被引：104

作者：

Rozenblatt-Rosen, Orit ^{[1
,2
]}

Nagaike, Takashi ^{[3
]}

Francis, Joshua M. ^{[1
,2
]}

Kaneko, Syuzo ^{[3
]}

Glatt, Karen A. ^{[1
,2
]}

Hughes, Christina M. ^{[1
,2
]}

LaFramboise, Thomas ^{[1
,2
]}

Manley, James L. ^{[3
]}

Meyerson, Matthew ^{[1
,2
]}

机构：

[1] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[3] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 03期

基金：

美国国家卫生研究院;

关键词：

HISTONE METHYLTRANSFERASE COMPLEX; POLYMERASE-II TRANSCRIPTION; HUMAN PAF COMPLEX; POLYADENYLATION FACTOR; ELONGATION-FACTORS; GENE-EXPRESSION; END FORMATION; PROTEIN; PARAFIBROMIN; HRPT2;

D O I：

10.1073/pnas.0812023106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The CDC73 tumor suppressor gene is mutationally inactivated in hereditary and sporadic parathyroid tumors. Its product, the Cdc73 protein, is a component of the RNA polymerase II and chromatin-associated human Paf1 complex (Paf1C). Here, we show that Cdc73 physically associates with the cleavage and polyadenylation specificity factor (CPSF) and cleavage stimulation factor (CstF) complexes that are required for the maturation of mRNA 3' ends in the cell nucleus. Immunodepletion experiments indicate that the Cdc73-CPSF-CstF complex is necessary for 3' mRNA processing in vitro. Microarray analysis of CDC73 siRNA-treated cells revealed INTS6, a gene encoding a subunit of the Integrator complex, as an in vivo Cdc73 target. Cdc73 depletion by siRNA resulted in decreased INTS6 mRNA abundance, and decreased association of CPSF and CstF subunits with the INTS6 locus. Our results suggest that Cdc73 facilitates association of 3' mRNA processing factors with actively-transcribed chromatin and support the importance of links between tumor suppression and mRNA maturation.

引用

页码：755 / 760

页数：6

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