The transcriptional elongation rate regulates alternative polyadenylation in yeast

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.经历二次生长响应（diauxic response）的酵母细胞，其poly(A)位点利用（poly(A) site utilization）呈现显著的上游偏移：多数基因因更多使用开放阅读框近端poly(A)位点（ORF-proximal poly(A) sites），进而生成更短的3’端mRNA异构体（3’ mRNA isoforms）。该改变后的poly(A)模式，与延伸速率减慢的RNA聚合酶II（Pol II）突变体细胞中观测到的模式极为相似。与之相反，携带延伸速率加快的Pol II突变体的细胞，其poly(A)位点则呈现细微的下游偏移。多数基因的聚腺苷酸化模式（polyadenylation patterns）对延伸速率的快慢均具有敏感性，且poly(A)利用的全局偏移与poly(A)位点侧翼序列（flanking poly(A) sites）的嘌呤含量升高显著相关。在二次生长响应的酵母细胞中，Pol II的持续合成能力（processivity）受损，但持续合成能力降低且Pol II延伸速率正常的菌株，其聚腺苷酸化谱仍维持正常状态。综上，Pol II的延伸速率对于poly(A)位点选择（poly(A) site selection）以及响应环境条件调控poly(A)模式均具有关键作用。