Year: 2024
Type: article
Abstract: A universal characteristic of eukaryotic transcription is that the promoter recruits RNAPII to produce both precursor mRNAs (pre-mRNAs) and short unstable promoter upstream transcripts (PROMPTs) toward the opposite direction. However, how the transcription machinery senses the correct direction to produce pre-mRNAs is largely unknown. Here, through multiple acute auxin-inducible degradation (AID) systems, we show that rapid depletion of a RNAPII-binding protein complex, Integrator, results in robust PROMPTsaccumulation throughout the genome. Interestingly, the accumulation of PROMPTs is compensated by the reduction of pre-mRNA transcripts in actively transcribed genes. Consistently, Integrator depletion alters the distribution of polymerase between the sense and antisense direction, which is marked by an increased RNAPII-CTD Tyr1 phosphorylation (Tyr1P) level at PROMPT regions and a refrained Ser2 phosphorylation (Ser2P) level at transcription start sites (TSSs). Mechanistically, the endonuclease activity of Integrator is critical to suppress PROMPTs production in a sequence-independent manner. During this step, the endonuclease activity can be inhibited by the U1 signal on nascent antisense transcripts through the recognition of the U1 snRNA-Integrator which relies on the U1-Integrator axis to govern the direction of gene transcription.
Authors: Jiao Yang, Jingyang Li, Langxi Miao, Xu Gao, Wenhao Sun, Shuo Linghu, Guiping Ren, Bangya Peng, Shunkai Chen, Zhongqi Liu, Bo Wang, Ao Dong, Duo Huang, Jinrong Yuan, Yunkun Dang, Fan Lai
Institution: Yunnan University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4395002509