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Journal article

Cisplatin exposure alters tRNA-derived small RNAs but does not affect epimutations in C. elegans

Abstract:

Background

The individual lifestyle and environment of an organism can influence its phenotype and potentially the phenotype of its offspring. The different genetic and non-genetic components of the inheritance system and their mutual interactions are key mechanisms to generate inherited phenotypic changes. Epigenetic changes can be transmitted between generations independently from changes in DNA sequence. In Caenorhabditis elegans, epigenetic differences, i.e. epimutations, mediated by small non-coding RNAs, particularly 22G-RNAs, as well as chromatin have been identified, and their average persistence is three to five generations. In addition, previous research showed that some epimutations had a longer duration and concerned genes that were enriched for multiple components of xenobiotic response pathways. These results raise the possibility that environmental stresses might change the rate at which epimutations occur, with potential significance for adaptation.

Results

In this work, we explore this question by propagating C. elegans lines either in control conditions or in moderate or high doses of cisplatin, which introduces genotoxic stress by damaging DNA. Our results show that cisplatin has a limited effect on global small non-coding RNA epimutations and epimutations in gene expression levels. However, cisplatin exposure leads to increased fluctuations in the levels of small non-coding RNAs derived from tRNA cleavage. We show that changes in tRNA-derived small RNAs may be associated with gene expression changes.

Conclusions

Our work shows that epimutations are not substantially altered by cisplatin exposure but identifies transient changes in tRNA-derived small RNAs as a potential source of variation induced by genotoxic stress.
Publication status:
Published
Peer review status:
Peer reviewed

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Files:
Publisher copy:
10.1186/s12915-023-01767-z

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author
ORCID:
0000-0003-0279-6199


More from this funder
Funding agency for:
Sarkies, P
Grant:
MC_UP_1102/13


Publisher:
BioMed Central
Journal:
BMC Biology More from this journal
Volume:
21
Issue:
1
Article number:
276
Place of publication:
England
Publication date:
2023-11-29
Acceptance date:
2023-11-13
DOI:
EISSN:
1741-7007
Pmid:
38031056


Language:
English
Keywords:
Pubs id:
1574582
Local pid:
pubs:1574582
Deposit date:
2024-04-05

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