Cellular imbalance of specific RNA-binding proteins associates with harmful R-loops.
Understanding how the assembly of nascent mRNA into a ribonucleoprotein (mRNP) influences R-loop homeostasis is crucial for gaining insight into the cellular mechanisms that prevent genome instability. Here, we identify three RNA-binding proteins, Rie1, Rim4 and She2, whose expression levels are imp...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-07-01
|
| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1011491 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849318421190148096 |
|---|---|
| author | José Antonio Mérida-Cerro Guillaume Chevreux Benoit Palancade Ana G Rondón Andrés Aguilera |
| author_facet | José Antonio Mérida-Cerro Guillaume Chevreux Benoit Palancade Ana G Rondón Andrés Aguilera |
| author_sort | José Antonio Mérida-Cerro |
| collection | DOAJ |
| description | Understanding how the assembly of nascent mRNA into a ribonucleoprotein (mRNP) influences R-loop homeostasis is crucial for gaining insight into the cellular mechanisms that prevent genome instability. Here, we identify three RNA-binding proteins, Rie1, Rim4 and She2, whose expression levels are important to limit R-loop accumulation and, thus, to prevent DNA damage. Interestingly, Rim4 and She2 are overrepresented in CBP80-containing mRNPs formed in the absence of THO. In addition, we found that an excess of the RNA exosome component Dis3 impairs its function, promoting R-loops, particularly from non-coding RNAs, which cause genomic instability. Our results indicate that changes in the availability of different RBPs or RNAs, causes R-loop-mediated DNA damage in the cell. These results may help to understand the mechanism that promotes cancer, as several RBPs are overexpressed in different types of tumors. |
| format | Article |
| id | doaj-art-c5b6c2be14be473c935b60c4e81b3ea4 |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-c5b6c2be14be473c935b60c4e81b3ea42025-08-20T03:50:50ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042025-07-01217e101149110.1371/journal.pgen.1011491Cellular imbalance of specific RNA-binding proteins associates with harmful R-loops.José Antonio Mérida-CerroGuillaume ChevreuxBenoit PalancadeAna G RondónAndrés AguileraUnderstanding how the assembly of nascent mRNA into a ribonucleoprotein (mRNP) influences R-loop homeostasis is crucial for gaining insight into the cellular mechanisms that prevent genome instability. Here, we identify three RNA-binding proteins, Rie1, Rim4 and She2, whose expression levels are important to limit R-loop accumulation and, thus, to prevent DNA damage. Interestingly, Rim4 and She2 are overrepresented in CBP80-containing mRNPs formed in the absence of THO. In addition, we found that an excess of the RNA exosome component Dis3 impairs its function, promoting R-loops, particularly from non-coding RNAs, which cause genomic instability. Our results indicate that changes in the availability of different RBPs or RNAs, causes R-loop-mediated DNA damage in the cell. These results may help to understand the mechanism that promotes cancer, as several RBPs are overexpressed in different types of tumors.https://doi.org/10.1371/journal.pgen.1011491 |
| spellingShingle | José Antonio Mérida-Cerro Guillaume Chevreux Benoit Palancade Ana G Rondón Andrés Aguilera Cellular imbalance of specific RNA-binding proteins associates with harmful R-loops. PLoS Genetics |
| title | Cellular imbalance of specific RNA-binding proteins associates with harmful R-loops. |
| title_full | Cellular imbalance of specific RNA-binding proteins associates with harmful R-loops. |
| title_fullStr | Cellular imbalance of specific RNA-binding proteins associates with harmful R-loops. |
| title_full_unstemmed | Cellular imbalance of specific RNA-binding proteins associates with harmful R-loops. |
| title_short | Cellular imbalance of specific RNA-binding proteins associates with harmful R-loops. |
| title_sort | cellular imbalance of specific rna binding proteins associates with harmful r loops |
| url | https://doi.org/10.1371/journal.pgen.1011491 |
| work_keys_str_mv | AT joseantoniomeridacerro cellularimbalanceofspecificrnabindingproteinsassociateswithharmfulrloops AT guillaumechevreux cellularimbalanceofspecificrnabindingproteinsassociateswithharmfulrloops AT benoitpalancade cellularimbalanceofspecificrnabindingproteinsassociateswithharmfulrloops AT anagrondon cellularimbalanceofspecificrnabindingproteinsassociateswithharmfulrloops AT andresaguilera cellularimbalanceofspecificrnabindingproteinsassociateswithharmfulrloops |