Tissue- and development-stage-specific mRNA and heterogeneous CNV signatures of human ribosomal proteins in normal and cancer samples.


Journal

Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011

Informations de publication

Date de publication:
27 07 2020
Historique:
accepted: 28 05 2020
revised: 20 05 2020
received: 05 11 2019
pubmed: 12 6 2020
medline: 24 9 2020
entrez: 12 6 2020
Statut: ppublish

Résumé

We give results from a detailed analysis of human Ribosomal Protein (RP) levels in normal and cancer samples and cell lines from large mRNA, copy number variation and ribosome profiling datasets. After normalizing total RP mRNA levels per sample, we find highly consistent tissue specific RP mRNA signatures in normal and tumor samples. Multiple RP mRNA-subtypes exist in several cancers, with significant survival and genomic differences. Some RP mRNA variations among subtypes correlate with copy number loss of RP genes. In kidney cancer, RP subtypes map to molecular subtypes related to cell-of-origin. Pan-cancer analysis of TCGA data showed widespread single/double copy loss of RP genes, without significantly affecting survival. In several cancer cell lines, CRISPR-Cas9 knockout of RP genes did not affect cell viability. Matched RP ribosome profiling and mRNA data in humans and rodents stratified by tissue and development stage and were strongly correlated, showing that RP translation rates were proportional to mRNA levels. In a small dataset of human adult and fetal tissues, RP protein levels showed development stage and tissue specific heterogeneity of RP levels. Our results suggest that heterogeneous RP levels play a significant functional role in cellular physiology, in both normal and disease states.

Identifiants

pubmed: 32525984
pii: 5856123
doi: 10.1093/nar/gkaa485
pmc: PMC7367157
doi:

Substances chimiques

RNA, Messenger 0
Ribosomal Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

7079-7098

Subventions

Organisme : NHGRI NIH HHS
ID : U41 HG001715
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM074024
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA194107
Pays : United States
Organisme : NHGRI NIH HHS
ID : P50 HG004233
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA233662
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA072720
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA226803
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA023100
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA232161
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217885
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA202752
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA248457
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA172513
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA220341
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG009285
Pays : United States
Organisme : NIDCR NIH HHS
ID : U01 DE028227
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE026870
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA209891
Pays : United States

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

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Auteurs

Anshuman Panda (A)

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.

Anupama Yadav (A)

Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Huwate Yeerna (H)

Moores Cancer Center, University of California San Diego, La Jolla, CA 92103, USA.

Amartya Singh (A)

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.

Michael Biehl (M)

Bernoulli Institute for Mathematics, Computer Science and Artificial Intelligence, University of Groningen, Nijenborgh 9, NL-9747 AG Groningen, The Netherlands.

Markus Lux (M)

Cognitive Interaction Technology (CITEC), Bielefeld University, Inspiration 1, D-33619 Bielefeld, Germany.

Alexander Schulz (A)

Cognitive Interaction Technology (CITEC), Bielefeld University, Inspiration 1, D-33619 Bielefeld, Germany.

Tyler Klecha (T)

Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ,08854, USA.

Sebastian Doniach (S)

Department of Applied Physics, Stanford University, Palo Alto, CA 94305, USA.

Hossein Khiabanian (H)

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.

Shridar Ganesan (S)

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.

Pablo Tamayo (P)

Moores Cancer Center, University of California San Diego, La Jolla, CA 92103, USA.
School of Medicine, University of California San Diego, La Jolla, CA 92093, USA.

Gyan Bhanot (G)

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
Moores Cancer Center, University of California San Diego, La Jolla, CA 92103, USA.
Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ,08854, USA.
Department of Physics and Astronomy, Rutgers University, Piscataway, NJ 08854, USA.

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Classifications MeSH