Transcription by RNA polymerase II (RNAPII) is a dynamic process with frequent variations in the elongation rate. However, the physiological relevance of variations in RNAPII elongation kinetics has remained unclear. Here we show in yeast that a RNAPII mutant that reduces the transcription elongation rate causes widespread changes in alternative polyadenylation (APA). We unveil two mechanisms by which APA affects gene expression in the slow mutant: 3′ UTR shortening and gene derepression by premature transcription termination of upstream interfering noncoding RNAs. Strikingly, the genes affected by these mechanisms are enriched for functions involved in phosphate uptake and purine synthesis, processes essential for maintenance of the intracellular nucleotide pool. As nucleotide concentration regulates transcription elongation, our findings argue that RNAPII is a sensor of nucleotide availability and that genes important for nucleotide pool maintenance have adopted regulatory mechanisms responsive to reduced rates of transcription elongation.

中文翻译：

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营养素依赖性的RNA聚合酶II延伸率控制通过可替代的聚腺苷酸化来调节特定的基因表达程序。

RNA聚合酶II（RNAPII）的转录是一个动态过程，其延伸率频繁变化。然而，RNAPII延伸动力学变化的生理相关性仍不清楚。在这里，我们在酵母中表明，降低转录伸长率的RNAPII突变体会导致替代性聚腺苷酸化（APA）发生广泛变化。我们揭示了APA影响慢突变体中基因表达的两种机制：3'UTR缩短和上游干扰非编码RNA的过早转录终止引起的基因抑制。引人注目的是，受这些机制影响的基因富集了与磷酸盐摄取和嘌呤合成有关的功能，这是维持细胞内核苷酸库必不可少的过程。由于核苷酸浓度调节转录延伸，