Recruitment of mRNA cleavage/polyadenylation machinery by the yeast chromatin protein Sin1p/Spt2p

Recruitment of mRNA cleavage/polyadenylation machinery by the yeast chromatin protein Sin1p/Spt2p
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DOI:
10.1073/pnas.0602014103
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发表时间:
2006-06-27
影响因子:
11.1
通讯作者:
Katcoff, Don J.
Katcoff, Don J.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hershkovits, Gitit;Bangio, Haim;Katcoff, Don J.

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酵母染色质蛋白Sin 1 p/Spt 2 p已经研究了很长时间,但对其功能的理解仍然难以捉摸。该蛋白质与HMG 1具有序列相似性,特异性结合交叉DNA结构,并作为SWI/SNF染色质重塑复合物激活的一个小家族基因的负转录调节因子。最近,它已被牵连在维持完整的染色质在转录延伸。在这里,我们提出的实验结果表明,Sin 1 p/Spt 2是必需的,并直接参与,有效的招聘的mRNA切割/聚腺苷酸化复合物。这一结论是基于以下发现:Sin 1 p/Spt 2经常特异性结合许多ORF的下游,但几乎总是第一个多聚腺苷酸化位点的上游。它直接与Fir 1 p相互作用,Fir 1 p是切割/多聚腺苷酸化复合物的一个组分。Sin 1 p/Spt 2 p的破坏导致mRNA上的poly(A)束缩短。它与Cdc 73 p一起具有合成致死性,Cdc 73 p参与复合物的募集。这份报告表明,染色质成分参与RNA的3'端加工。
The yeast chromatin protein Sin1p/Spt2p has long been studied, but the understanding of its function has remained elusive. The protein has sequence similarity to HMG1, specifically binds crossing DNA structures, and serves as a negative transcriptional regulator of a small family of genes that are activated by the SWI/SNF chromatin-remodeling complex. Recently, it has been implicated in maintaining the integrity of chromatin during transcription elongation. Here we present experiments whose results indicate that Sin1p/Spt2 is required for, and is directly involved in, the efficient recruitment of the mRNA cleavage/polyadenylation complex. This conclusion is based on the following findings: Sin1p/Spt2 frequently binds specifically downstream of many ORFs but almost always upstream of the first polyadenylation site. It directly interacts with Fir1p, a component of the cleavage/polyadenylation complex. Disruption of Sin1p/Spt2p results in foreshortened poly(A) tracts on mRNA. It is synthetically lethal with Cdc73p, which is involved in the recruitment of the complex. This report shows that a chromatin component is involved in 3' end processing of RNA.