Functional unknomics: Systematic screening of conserved genes of unknown function.
Journal
PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
12
01
2023
accepted:
27
06
2023
medline:
10
8
2023
pubmed:
8
8
2023
entrez:
8
8
2023
Statut:
epublish
Résumé
The human genome encodes approximately 20,000 proteins, many still uncharacterised. It has become clear that scientific research tends to focus on well-studied proteins, leading to a concern that poorly understood genes are unjustifiably neglected. To address this, we have developed a publicly available and customisable "Unknome database" that ranks proteins based on how little is known about them. We applied RNA interference (RNAi) in Drosophila to 260 unknown genes that are conserved between flies and humans. Knockdown of some genes resulted in loss of viability, and functional screening of the rest revealed hits for fertility, development, locomotion, protein quality control, and resilience to stress. CRISPR/Cas9 gene disruption validated a component of Notch signalling and 2 genes contributing to male fertility. Our work illustrates the importance of poorly understood genes, provides a resource to accelerate future research, and highlights a need to support database curation to ensure that misannotation does not erode our awareness of our own ignorance.
Identifiants
pubmed: 37552676
doi: 10.1371/journal.pbio.3002222
pii: PBIOLOGY-D-23-00105
pmc: PMC10409296
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3002222Subventions
Organisme : Medical Research Council
ID : MC_U105178780
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 101035/Z/13/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U105178780
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 220887/Z/20/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U105178783
Pays : United Kingdom
Informations de copyright
Copyright: © 2023 Rocha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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