Tsinghua University School of Medicine, Beijing 100084, China.
Peking University-Tsinghua Center for Life Sciences, Beijing 100084, China; Institute for Immunology, Tsinghua University School of Medicine, Beijing 100084, China.
Cell Rep. 2022 Mar 15;38(11):110519. doi: 10.1016/j.celrep.2022.110519.
The PAF1 complex (PAF1C) functions in multiple transcriptional processes involving RNA polymerase II (RNA Pol II). Enhancer RNAs (eRNAs) and promoter upstream transcripts (PROMPTs) are pervasive transcripts transcribed by RNA Pol II and degraded rapidly by the nuclear exosome complex after 3' endonucleolytic cleavage by the Integrator complex (Integrator). Here we show that PAF1C has a role in termination of eRNAs and PROMPTs that are cleaved 1-3 kb downstream of the transcription start site. Mechanistically, PAF1C facilitates recruitment of Integrator to sites of pervasive transcript cleavage, promoting timely cleavage and transcription termination. We also show that PAF1C recruits Integrator to coding genes, where PAF1C then dissociates from Integrator upon entry into processive elongation. Our results demonstrate a function of PAF1C in limiting the length and accumulation of pervasive transcripts that result from non-productive transcription.
PAF1 复合物（PAF1C）在涉及 RNA 聚合酶 II（RNA Pol II）的多种转录过程中发挥作用。增强子 RNA（eRNA）和启动子上游转录物（PROMPT）是由 RNA Pol II 转录的普遍转录物，在 Integrator 复合物（Integrator）进行 3' 内切核酸酶切割后，被核 exosome 复合物迅速降解。在这里，我们表明 PAF1C 在终止 eRNA 和 PROMPT 的转录中发挥作用，这些转录物在转录起始位点下游 1-3 kb 处被切割。从机制上讲，PAF1C 促进 Integrator 招募到普遍转录物切割的位点，从而促进及时的切割和转录终止。我们还表明，PAF1C 将 Integrator 招募到编码基因，然后在进入持续延伸时，PAF1C 从 Integrator 上解离。我们的结果表明 PAF1C 在限制非生产性转录产生的普遍转录物的长度和积累方面发挥作用。
