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Cited by 208RNA and protein synthesis mechanismsRNA Research and SplicingGenetic Associations and Epidemiology

Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans

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Cenik, Can, Cenik, Elif Sarinay, Byeon, Gun W., Grubert, Fabian, Candille, Sophie I., Spacek, Damek, Alsallakh, Bilal, Tilgner, Hagen +4 more·2015·Genome Research
DOI 10.1101/gr.193342.115PMC PMC4617958

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Abstract

Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding, and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy—many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation.

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  • How 5′ UTR sequences affect translation is only beginning to be understood.

    “Genetic variants play a major role in phenotypic differences between individuals38 and how these sequences affect translation is only beginning to be understood39,40.”

    From Human 5′ UTR design and variant effect prediction from a massively parallel translation assay (2019) · cites this paper as [40]

    The Discussion (page unavailable) says the molecular mechanisms linking sequence to translation remain an interesting question and that less is known about positive regulation by upstream open reading frames. The Results show that 5′ UTR variants affect translation, but the paper does not characterize understanding of all 5′ UTR sequence effects as only beginning. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

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Authors
Cenik, C., Cenik, E. S., Byeon, G. W., Grubert, F., Candille, S. I., Spacek, D., Alsallakh, B., Tilgner, H., Araya, C. L., Tang, H., Ricci, E., & Snyder, M. P.
Affiliations
  • Stanford Medicine (US)
  • TU Wien (AT)
  • Inserm (FR)
Corresponding author
Snyder, Michael P.
ORCID
Venue
Genome Research
Publisher
Cold Spring Harbor Laboratory
Published
2015-08-21
Volume
25
Issue
11
Pages
1610-1621
ISSN
  • 1088-9051 (ISSN-L)
  • 1549-5469
DOI
10.1101/gr.193342.115
PMC
PMC4617958
OpenAlex
W1906706885
Cited by
208
References
15
Citations by year
2026: 13 · 2025: 14 · 2024: 23 · 2023: 14 · 2022: 20 · 2021: 28 · 2020: 16 · 2019: 22 · 2018: 23 · 2017: 14 · 2016: 20 · 2015: 1
Type
posted content
Language
en
Open access
Licence
other-oa
Locations
  • Genome Research (publishedVersion, other-oa)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion, cc-by-nc-nd)
  • eScholarship@UMassChan (submittedVersion, cc-by)
  • HAL (submittedVersion, other-oa)
Funders
  • Child Health Research Institute (UL1TR000093)
  • Benchmark Stanford Graduate
  • Stanford Transformative and Innovation grant
  • National Institutes of Health
  • National Human Genome Research Institute (NIH/NHGRI T32, HG000044)
  • NIH (GM07305907, 1U01HG00761101, HG007611, HG006996)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
translational regulation, ribosome profiling, ribosome occupancy, protein abundance, genetic variants, lymphoblastoid cell lines, upstream open reading frames, start codon, personalized medicine, phenotypic diversity
MeSH terms
Chromatin, Gene Expression Regulation, Humans, Ribosomes, RNA, RNA, Messenger, Protein Biosynthesis, Sequence Alignment, Sequence Analysis, RNA, Polymorphism, Single Nucleotide, Gene Expression Profiling, Quantitative Trait Loci, Proteomics

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