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标题：Antagonistic cotranscriptional regulation through ARGONAUTE1 and the THO/TREX complex orchestrates FLC transcriptional output
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作者：Congyao Xu ; Xiaofeng Fang ; Tiancong Lu 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：47
DOI：10.1073/pnas.2113757118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance RNA processing generally occurs as transcripts are being produced and the concomitant cotranscriptional processes are interconnected with chromatin regulation. These cotranscriptional mechanisms quantitatively influence transcriptional output. At the Arabidopsis gene FLC, repression involves alternative processing of FLC antisense transcripts linked to delivery of a local chromatin environment that determines FLC transcription initiation and elongation rate. Here, we show that AGO1, a factor known predominantly for its role in posttranscriptional gene silencing, is involved in this cotranscriptional repression mechanism. Conserved cotranscriptional regulators, the THO/TREX complex and NTC components of the activated spliceosome, physically associate with AGO1. Our analysis suggests that alternative interactions of cotranscriptional regulators with the RNA Pol II–spliceosome link RNA processing and chromatin modification to quantitatively regulate transcriptional output. Quantitative transcriptional control is essential for physiological and developmental processes in many organisms. Transcriptional output is influenced by cotranscriptional processes interconnected to chromatin regulation, but how the functions of different cotranscriptional regulators are integrated is poorly understood. The Arabidopsis floral repressor locus FLOWERING LOCUS C ( FLC) is cotranscriptionally repressed by alternative processing of the antisense transcript COOLAIR. Proximal 3′-end processing of COOLAIR resolves a cotranscriptionally formed R-loop, and this process physically links to a histone-modifying complex FLD/SDG26/LD. This induces a chromatin environment locally that determines low transcription initiation and a slow elongation rate to both sense and antisense strands. Here, we show that ARGONAUTE1 (AGO1) genetically functions in this cotranscriptional repression mechanism. AGO1 associates with COOLAIR and influences COOLAIR splicing dynamics to promote proximal COOLAIR, R-loop resolution, and chromatin silencing. Proteomic analyses revealed physical associations between AGO1, subunits of RNA Polymerase II (Pol II), the splicing-related proteins—the spliceosome NineTeen Complex (NTC) and related proteins (NTR)—and the THO/TREX complex. We connect these activities by demonstrating that the THO/TREX complex activates FLC expression acting antagonistically to AGO1 in COOLAIR processing. Together these data reveal that antagonistic cotranscriptional regulation through AGO1 or THO/TREX influences COOLAIR processing to deliver a local chromatin environment that determines FLC transcriptional output. The involvement of these conserved cotranscriptional regulators suggests similar mechanisms may underpin quantitative transcriptional regulation generally.
关键词：RNA processing; ARGONAUTE1; THO/TREX complex; cotranscription