Artículo
Rat1 promotes premature transcription termination at R-loops
Autor/es | Mérida Cerro, José Antonio
Maraver-Cárdenas, Pablo García Rondón, Ana Aguilera López, Andrés |
Departamento | Universidad de Sevilla. Departamento de Genética |
Fecha de publicación | 2024-04-24 |
Fecha de depósito | 2024-05-31 |
Publicado en |
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Resumen | 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 ... 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 str uct ures f ormed b y 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 y east. Importantly, w e demonstrate that the Rat1 transcription terminator factor facilitates transcription throughout such str uct ures by inducing premature termination of arrested RNAPIIs. We propose that RNase H degrades the RNA moiety of the hybrid, pro viding an entry site for Rat1. T hus, w e ha v e unco v ered an unanticipated function of Rat1 as a transcription restoring f actor opening up the possibility that it ma y also promote transcription through other genomic DNA str uct ures intrinsically difficult to transcribe. If R-loop-mediated transcriptional stress is not relie v ed b y Rat1, it will cause genomic inst abilit y, probably through the increase of transcription-replication conflicts, a deleterious situation that could lead to cancer. |
Agencias financiadoras | Ministerio de Ciencia e Innovación (MICIN). España Agencia Estatal de Investigación. España Junta de Andalucía |
Identificador del proyecto | PID2019-104270GB-I00
P18-FR-655 |
Cita | Mérida Cerro, J.A., Maraver-Cárdenas, P., García Rondón, A. y Aguilera López, A. (2024). Rat1 promotes premature transcription termination at R-loops. Nucleic Acids Research, 52 (7), 3623-3635. https://doi.org/10.1093/nar/gkae033. |
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