Pause sites promote transcriptional termination of mammalian RNA polymerase II

被引:150
作者
Gromak, Natalia [1 ]
West, Steven [1 ]
Proudfoot, Nick J. [1 ]
机构
[1] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
D O I
10.1128/MCB.26.10.3986-3996.2006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Polymerase II (Pol II) transcriptional termination depends on two independent genetic elements: poly(A) signals and downstream terminator sequences. The latter may either promote cotranscriptional RNA cleavage or pause elongating Pol II. We demonstrate that the previously characterized MAZ(4) pause element promotes Pol II termination downstream of a poly(A) signal, dependent on both the proximity of the pause site and poly(A) signal and the strength of the poly(A) signal. The 5'-> 3' exonuclease Xrn2 facilitates this pause-dependent termination by degrading the 3' product of poly(A) site cleavage. The human beta-actin gene also possesses poly(A) site proximal pause sequences, which like MAZ(4) are G rich and promote transcriptional termination. Xrn2 depletion causes an increase in both steady-state RNA and Pol II levels downstream of the beta-actin poly(A) site. Taken together, we provide new insights into the mechanism of pause site-mediated termination and establish a general role for the 5'-> 3' exonuclease Xrn2 in Pol II termination.
引用
收藏
页码:3986 / 3996
页数:11
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