4.8 Article

Antagonistic cotranscriptional regulation through ARGONAUTE1 and the THO/TREX complex orchestrates FLC transcriptional output

出版社

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2113757118

关键词

RNA processing; ARGONAUTE1; THO/TREX complex; cotranscription

资金

  1. European Research Council grant EPISWITCH [833254]
  2. Royal Society Professorship [RP\R1\180002]
  3. Biotechnology and Biological Sciences Research Council Institute Strategic Programme GEN [BB/P013511/1]
  4. Wellcome Senior Investigator grant [210654]
  5. European Research Council (ERC) [833254] Funding Source: European Research Council (ERC)

向作者/读者索取更多资源

The study reveals that the Arabidopsis floral repressor gene FLC is co-transcriptionally repressed by COOLAIR, with the involvement of AGO1 in promoting COOLAIR splicing dynamics and chromatin silencing. AGO1 is shown to associate with COOLAIR and influence its processing, leading to the resolution of R-loops and local chromatin environment conducive to low transcription initiation. These findings suggest a conserved cotranscriptional regulation mechanism involving AGO1 that influences 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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