The best-studied mechanism of eukaryotic RNA polymerase II (RNAPII) transcriptional termination involves polyadenylation site-directed cleavage of the nascent RNA. The RNAPII-associated cleavage product is then degraded by XRN2, dislodging RNAPII from the DNA template. In contrast, prokaryotic RNAP and eukaryotic RNAPIII often terminate directly at T-tracts in the coding DNA strand. Here, we demonstrate a similar and omnipresent capability for mammalian RNAPII. Importantly, this termination mechanism does not require upstream RNA cleavage. Accordingly, T-tract-dependent termination can take place when XRN2 cannot be engaged. We show that T-tracts can terminate snRNA transcription independently of RNA cleavage by the Integrator complex. Importantly, we found genome-wide termination at T-tracts in promoter-proximal regions but not within protein-coding gene bodies. XRN2-dependent termination dominates downstream from protein-coding genes, but the T-tract process is sometimes used. Overall, we demonstrate global DNA-directed attrition of RNAPII transcription, suggesting that RNAPs retain the potential to terminate over T-rich sequences throughout evolution.

中文翻译：

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哺乳动物 RNA 聚合酶 II 的 DNA 定向终止


真核 RNA 聚合酶 II （RNAPII） 转录终止研究最深入的机制涉及新生 RNA 的聚腺苷酸化定点切割。然后 RNAPII 相关切割产物被 XRN2 降解，使 RNAPII 从 DNA 模板中脱落。相比之下，原核 RNAP 和真核 RNAPIII 通常直接终止于编码 DNA 链中的 T 束。在这里，我们展示了哺乳动物 RNAPII 的相似且无处不在的能力。重要的是，这种终止机制不需要上游 RNA 切割。因此，当 XRN2 无法接合时，可以发生 T 束依赖性终止。我们表明 T 束可以独立于 Integrator 复合物的 RNA 切割终止 snRNA 转录。重要的是，我们发现启动子近端区域的 T 束处存在全基因组终止，但在蛋白质编码基因体内没有。XRN2 依赖性终止在蛋白质编码基因的下游占主导地位，但有时使用 T 束过程。总体而言，我们证明了 RNAPII 转录的整体 DNA 定向损耗，表明 RNAP 在整个进化过程中保留了终止富含 T 的序列的潜力。