Genetic compensation triggered by mutant mRNA degradation.
Journal
Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
03
12
2017
accepted:
05
02
2019
pubmed:
5
4
2019
medline:
4
12
2019
entrez:
5
4
2019
Statut:
ppublish
Résumé
Genetic robustness, or the ability of an organism to maintain fitness in the presence of harmful mutations, can be achieved via protein feedback loops. Previous work has suggested that organisms may also respond to mutations by transcriptional adaptation, a process by which related gene(s) are upregulated independently of protein feedback loops. However, the prevalence of transcriptional adaptation and its underlying molecular mechanisms are unknown. Here, by analysing several models of transcriptional adaptation in zebrafish and mouse, we uncover a requirement for mutant mRNA degradation. Alleles that fail to transcribe the mutated gene do not exhibit transcriptional adaptation, and these alleles give rise to more severe phenotypes than alleles displaying mutant mRNA decay. Transcriptome analysis in alleles displaying mutant mRNA decay reveals the upregulation of a substantial proportion of the genes that exhibit sequence similarity with the mutated gene's mRNA, suggesting a sequence-dependent mechanism. These findings have implications for our understanding of disease-causing mutations, and will help in the design of mutant alleles with minimal transcriptional adaptation-derived compensation.
Identifiants
pubmed: 30944477
doi: 10.1038/s41586-019-1064-z
pii: 10.1038/s41586-019-1064-z
pmc: PMC6707827
mid: EMS81644
doi:
Substances chimiques
Histones
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
193-197Subventions
Organisme : European Research Council
ID : 694455
Pays : International
Commentaires et corrections
Type : CommentIn
Type : CommentIn
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