Document Detail

Genetic variation shapes protein networks mainly through non-transcriptional mechanisms.
MedLine Citation:
PMID:  21909241     Owner:  NLM     Status:  MEDLINE    
Networks of co-regulated transcripts in genetically diverse populations have been studied extensively, but little is known about the degree to which these networks cause similar co-variation at the protein level. We quantified 354 proteins in a genetically diverse population of yeast segregants, which allowed for the first time construction of a coherent protein co-variation matrix. We identified tightly co-regulated groups of 36 and 93 proteins that were made up predominantly of genes involved in ribosome biogenesis and amino acid metabolism, respectively. Even though the ribosomal genes were tightly co-regulated at both the protein and transcript levels, genetic regulation of proteins was entirely distinct from that of transcripts, and almost no genes in this network showed a significant correlation between protein and transcript levels. This result calls into question the widely held belief that in yeast, as opposed to higher eukaryotes, ribosomal protein levels are regulated primarily by regulating transcript levels. Furthermore, although genetic regulation of the amino acid network was more similar for proteins and transcripts, regression analysis demonstrated that even here, proteins vary predominantly as a result of non-transcriptional variation. We also found that cis regulation, which is common in the transcriptome, is rare at the level of the proteome. We conclude that most inter-individual variation in levels of these particular high abundance proteins in this genetically diverse population is not caused by variation of their underlying transcripts.
Eric J Foss; Dragan Radulovic; Scott A Shaffer; David R Goodlett; Leonid Kruglyak; Antonio Bedalov
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-09-06
Journal Detail:
Title:  PLoS biology     Volume:  9     ISSN:  1545-7885     ISO Abbreviation:  PLoS Biol.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-12     Completed Date:  2012-01-05     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101183755     Medline TA:  PLoS Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1001144     Citation Subset:  IM    
Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.
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MeSH Terms
Chromosome Segregation
Gene Expression Profiling
Genetic Variation*
Protein Interaction Mapping / methods*
Proteome / genetics*
Quantitative Trait, Heritable
RNA, Messenger / metabolism
Ribosomes / genetics
Transcription, Genetic*
Yeasts / genetics*,  metabolism
Grant Support
5 P30 CA015704/CA/NCI NIH HHS; CA015704/CA/NCI NIH HHS; CA129132/CA/NCI NIH HHS; R01 CA129132-05/CA/NCI NIH HHS; R33CA099139-04/CA/NCI NIH HHS; R37 MH059520/MH/NIMH NIH HHS; UL1 RR025014/RR/NCRR NIH HHS; UL1RR025014/RR/NCRR NIH HHS
Reg. No./Substance:
0/Proteome; 0/RNA, Messenger
Comment In:
PLoS Biol. 2011 Sep;9(9):e1001146   [PMID:  21909242 ]

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