Antagonistic cotranscriptional regulation through ARGONAUTE1 and the THO/TREX complex orchestrates FLC transcriptional output.
Antagonistic cotranscriptional regulation through ARGONAUTE1 and the THO/TREX complex orchestrates FLC transcriptional output.
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DOI：
10.1073/pnas.2113757118
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发表时间：
2021-11-23
影响因子：
11.1
通讯作者：
Dean C
中科院分区：
文献类型：
--
作者：
Xu C;Fang X;Lu T;Dean C
RNA 加工通常在转录物产生时发生，并且伴随的共转录过程与染色质调控相互关联。这些共转录机制定量地影响转录输出。在拟南芥基因 FLC 中，抑制涉及 FLC 反义转录物的替代处理，该处理与决定 FLC 转录起始和延伸率的局部染色质环境的传递相关。在这里，我们发现 AGO1（一种主要因其在转录后基因沉默中的作用而闻名的因子）参与了这种共转录抑制机制。保守的共转录调节因子、激活剪接体的 THO/TREX 复合物和 NTC 成分与 AGO1 物理关联。我们的分析表明，共转录调节因子与 RNA Pol II 剪接体的替代相互作用将 RNA 加工和染色质修饰联系起来，从而定量调节转录输出。定量转录控制对于许多生物体的生理和发育过程至关重要。转录输出受到与染色质调控相关的共转录过程的影响，但不同共转录调节因子的功能如何整合尚不清楚。拟南芥花抑制基因座 FLOWERING LOCUS C (FLC) 通过反义转录本 COOLAIR 的选择性加工进行共转录抑制。 COOLAIR 的近端 3' 端加工解析了共转录形成的 R 环，并且该过程在物理上连接到组蛋白修饰复合物 FLD/SDG26/LD。这会在局部诱导染色质环境，决定低转录起始和有义链和反义链的缓慢延伸率。在这里，我们证明了 ARGONAUTE1 (AGO1) 在这种共转录抑制机制中发挥遗传作用。 AGO1 与 COOLAIR 结合并影响 COOLAIR 剪接动力学，以促进近端 COOLAIR、R 环分辨率和染色质沉默。蛋白质组学分析揭示了 AGO1、RNA 聚合酶 II (Pol II) 亚基、剪接相关蛋白（剪接体 NineTeen 复合物 (NTC) 和相关蛋白 (NTR)）以及 THO/TREX 复合物之间的物理关联。我们通过证明 THO/TREX 复合物激活 FLC 表达来将这些活动联系起来，FLC 表达在 COOLAIR 处理中与 AGO1 拮抗。这些数据共同表明，通过 AGO1 或 THO/TREX 的拮抗共转录调节会影响 COOLAIR 处理，以提供决定 FLC 转录输出的局部染色质环境。这些保守的共转录调节因子的参与表明类似的机制可能普遍支持定量转录调节。
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.
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Argonaute在人核RNA中结合及其对替代剪接的影响。
DOI：
10.1261/rna.078707.121
发表时间：
2021-09
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Chu Y;Yokota S;Liu J;Kilikevicius A;Johnson KC;Corey DR
通讯作者：
Corey DR
DOI：
10.1038/nrg3355
发表时间：
2013-02
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.8
作者：
Cernilogar, Filippo M.;Onorati, Maria Cristina;Kothe, Greg O.;Burroughs, A. Maxwell;Parsi, Krishna Mohan;Breiling, Achim;Lo Sardo, Federica;Saxena, Alka;Miyoshi, Keita;Siomi, Haruhiko;Siomi, Mikiko C.;Carninci, Piero;Gilmour, David S.;Corona, Davide F. V.;Orlando, Valerio
通讯作者：
Orlando, Valerio
影响因子：
64.5
作者：
Halic M;Moazed D
通讯作者：
Moazed D
拟南芥 ARGONAUTE 1 结合染色质促进基因转录以响应激素和应激
影响因子：
11.8
作者：
Liu, Chang;Xin, Ying;Qi, Yijun
通讯作者：
Qi, Yijun