Proteogenomic analysis of cancer aneuploidy and normal tissues reveals divergent modes of gene regulation across cellular pathways.
aneuploidy
cancer
cancer biology
computational biology
gene expression
human
protein regulation
proteogenomic
systems biology
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
21 09 2022
21 09 2022
Historique:
received:
03
11
2021
accepted:
15
08
2022
entrez:
21
9
2022
pubmed:
22
9
2022
medline:
24
9
2022
Statut:
epublish
Résumé
How cells control gene expression is a fundamental question. The relative contribution of protein-level and RNA-level regulation to this process remains unclear. Here, we perform a proteogenomic analysis of tumors and untransformed cells containing somatic copy number alterations (SCNAs). By revealing how cells regulate RNA and protein abundances of genes with SCNAs, we provide insights into the rules of gene regulation. Protein complex genes have a strong protein-level regulation while non-complex genes have a strong RNA-level regulation. Notable exceptions are plasma membrane protein complex genes, which show a weak protein-level regulation and a stronger RNA-level regulation. Strikingly, we find a strong negative association between the degree of RNA-level and protein-level regulation across genes and cellular pathways. Moreover, genes participating in the same pathway show a similar degree of RNA- and protein-level regulation. Pathways including translation, splicing, RNA processing, and mitochondrial function show a stronger protein-level regulation while cell adhesion and migration pathways show a stronger RNA-level regulation. These results suggest that the evolution of gene regulation is shaped by functional constraints and that many cellular pathways tend to evolve one predominant mechanism of gene regulation at the protein level or at the RNA level.
Identifiants
pubmed: 36129397
doi: 10.7554/eLife.75227
pii: 75227
pmc: PMC9491860
doi:
pii:
Substances chimiques
Membrane Proteins
0
RNA
63231-63-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P30 CA016087
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM136542
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA248631
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA212621
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210972
Pays : United States
Organisme : Cancer Research UK
ID : C5470/A27144
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : K99 CA212621
Pays : United States
Informations de copyright
© 2022, Cheng, Zhao, Katsnelson et al.
Déclaration de conflit d'intérêts
PC, XZ, LK, EC, AM, JM, SL, RR, RM, JS, DG, DF, TD No competing interests declared
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