Rat1 promotes premature transcription termination at R-loops.

Autor:	Mérida-Cerro JA; Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla, CSIC, 41092 Seville, Spain; Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Seville, Spain., Maraver-Cárdenas P; Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla, CSIC, 41092 Seville, Spain; Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Seville, Spain., Rondón AG; Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla, CSIC, 41092 Seville, Spain; Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Seville, Spain., Aguilera A; Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla, CSIC, 41092 Seville, Spain; Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Seville, Spain.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Apr 24; Vol. 52 (7), pp. 3623-3635.
DOI:	10.1093/nar/gkae033
Abstrakt:	Certain DNA sequences can adopt a non-B form in the genome that interfere with DNA-templated processes, including transcription. Among the sequences that are intrinsically difficult to transcribe are those that tend to form R-loops, three-stranded nucleic acid structures formed by a DNA-RNA hybrid and the displaced ssDNA. Here we compared the transcription of an endogenous gene with and without an R-loop-forming sequence inserted. We show that, in agreement with previous in vivo and in vitro analyses, transcription elongation is delayed by R-loops in yeast. Importantly, we demonstrate that the Rat1 transcription terminator factor facilitates transcription throughout such structures by inducing premature termination of arrested RNAPIIs. We propose that RNase H degrades the RNA moiety of the hybrid, providing an entry site for Rat1. Thus, we have uncovered an unanticipated function of Rat1 as a transcription restoring factor opening up the possibility that it may also promote transcription through other genomic DNA structures intrinsically difficult to transcribe. If R-loop-mediated transcriptional stress is not relieved by Rat1, it will cause genomic instability, probably through the increase of transcription-replication conflicts, a deleterious situation that could lead to cancer. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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