Literature DB >> 32525984

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

Anshuman Panda1, Anupama Yadav2,3,4, Huwate Yeerna5, Amartya Singh1, Michael Biehl6, Markus Lux7, Alexander Schulz7, Tyler Klecha8, Sebastian Doniach9, Hossein Khiabanian1, Shridar Ganesan1, Pablo Tamayo5,10, Gyan Bhanot1,5,8,11.   

Abstract

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

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Year:  2020        PMID: 32525984      PMCID: PMC7367157          DOI: 10.1093/nar/gkaa485

Source DB:  PubMed          Journal:  Nucleic Acids Res        ISSN: 0305-1048            Impact factor:   16.971


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