The transcriptional elongation rate regulates alternative polyadenylation in yeast.
The transcriptional elongation rate regulates alternative polyadenylation in yeast.
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DOI：
10.7554/elife.59810
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发表时间：
2020-08-26
期刊：
影响因子：
7.7
通讯作者：
Struhl K
中科院分区：
文献类型：
--
作者：
Geisberg JV;Moqtaderi Z;Struhl K
经历二次扩增反应的酵母细胞显示poly（A）位点利用的显著上游移位，ORF近端poly（A）位点的使用增加导致大多数基因的3' mRNA同种型变短。这种改变的poly（A）模式与在含有具有缓慢延伸速率的Pol II衍生物的细胞中观察到的极为相似。相反，含有具有快速延伸速率的衍生物的细胞显示poly（A）位点的微妙下游移位。许多基因的多聚腺苷酸化模式对快速和缓慢的延伸速率都很敏感，并且多聚腺苷酸利用率的整体变化与多聚腺苷酸位点侧翼序列的嘌呤含量增加密切相关。Pol II的持续合成能力在二次细胞中受损，但具有降低的持续合成能力和正常Pol II延伸率的菌株具有正常的多聚腺苷酸化特征。因此，Pol II延伸速度对于poly（A）位点选择和响应环境条件调节poly（A）模式是重要的。
Yeast cells undergoing the diauxic response show a striking upstream shift in poly(A) site utilization, with increased use of ORF-proximal poly(A) sites resulting in shorter 3’ mRNA isoforms for most genes. This altered poly(A) pattern is extremely similar to that observed in cells containing Pol II derivatives with slow elongation rates. Conversely, cells containing derivatives with fast elongation rates show a subtle downstream shift in poly(A) sites. Polyadenylation patterns of many genes are sensitive to both fast and slow elongation rates, and a global shift of poly(A) utilization is strongly linked to increased purine content of sequences flanking poly(A) sites. Pol II processivity is impaired in diauxic cells, but strains with reduced processivity and normal Pol II elongation rates have normal polyadenylation profiles. Thus, Pol II elongation speed is important for poly(A) site selection and for regulating poly(A) patterns in response to environmental conditions.