Regulation of alternative polyadenylation in the yeast Saccharomyces cerevisiae by histone H3K4 and H3K36 methyltransferases
Regulation of alternative polyadenylation in the yeast Saccharomyces cerevisiae by histone H3K4 and H3K36 methyltransferases
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DOI：
10.1093/nar/gkaa292
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发表时间：
2020-06-04
影响因子：
14.9
通讯作者：
Moore, Claire L.
中科院分区：
文献类型：
--
作者：
Michaels, Katarzyna Kaczmarek;Mostafa, Salwa Mohd;Moore, Claire L.
通过表观遗传修饰调整DNA结构，改变前体mRNA裂解和聚腺苷化的聚腺苷化（pA）位点，使细胞能够快速应对环境应激。由于多聚腺苷酸化发生共转录，核小体定位和染色质修饰的特定模式与pA位点的使用相关，表观遗传因素可能影响选择性多聚腺苷酸化（APA）。我们报道了组蛋白H3K4甲基转移酶Set1和组蛋白H3K36甲基转移酶Set2控制酿酒酵母（Saccharomyces cerevisiae）中pA位点的选择，酿酒酵母是研究进化保守的真核生物过程的强大模型。SET1或SET2的缺失导致RNA聚合酶II (RNAP II) c端区域丝氨酸-2磷酸化增加，以及切割/聚腺苷化复合物的招募增加，这两者都可能导致观察到的pA位点使用的改变。化学抑制TOR信号，导致营养应激，导致依赖Set1-和set2的APA。此外，Set1和Set2降低了单个pA位点的利用效率，并控制了pA位点周围核小体的占用。总的来说，我们的研究表明，甲基转移酶Set1和Set2调节营养胁迫诱导的APA，影响RNAP II c端结构域Ser2的磷酸化，并控制3'端加工机制向pA位点附近的招募。
Adjusting DNA structure via epigenetic modifications, and altering polyadenylation (pA) sites at which precursor mRNA is cleaved and polyadenylated, allows cells to quickly respond to environmental stress. Since polyadenylation occurs co-transcriptionally, and specific patterns of nucleosome positioning and chromatin modifications correlate with pA site usage, epigenetic factors potentially affect alternative polyadenylation (APA). We report that the histone H3K4 methyltransferase Set1, and the histone H3K36 methyltransferase Set2, control choice of pA site in Saccharomyces cerevisiae, a powerful model for studying evolutionarily conserved eukaryotic processes. Deletion of SET1 or SET2 causes an increase in serine-2 phosphorylation within the C-terminal domain of RNA polymerase II (RNAP II) and in the recruitment of the cleavage/polyadenylation complex, both of which could cause the observed switch in pA site usage. Chemical inhibition of TOR signaling, which causes nutritional stress, results in Set1- and Set2-dependent APA. In addition, Set1 and Set2 decrease efficiency of using single pA sites, and control nucleosome occupancy around pA sites. Overall, our study suggests that the methyltransferases Set1 and Set2 regulate APA induced by nutritional stress, affect the RNAP II C-terminal domain phosphorylation at Ser2, and control recruitment of the 3' end processing machinery to the vicinity of pA sites.