Tissue- and development-stage-specific mRNA and heterogeneous CNV signatures of human ribosomal proteins in normal and cancer samples
Autor: | Anshuman Panda, Huwate Yeerna, Anupama Yadav, Tyler Klecha, Hossein Khiabanian, Markus Lux, Shridar Ganesan, Pablo Tamayo, Gyan Bhanot, Sebastian Doniach, Alexander Schulz, Michael Biehl, Amartya Singh |
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Přispěvatelé: | Intelligent Systems |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Ribosomal Proteins
DNA Copy Number Variations AcademicSubjects/SCI00010 Biology Cell Line 03 medical and health sciences Mice 0302 clinical medicine Fetus Ribosomal protein Neoplasms Databases Genetic Genetics medicine Protein biosynthesis Animals Humans Ribosome profiling Copy-number variation RNA Messenger Gene 030304 developmental biology 0303 health sciences Messenger RNA Cancer Computational Biology Gene Expression Regulation Developmental Translation (biology) medicine.disease Molecular biology Gene Expression Regulation Neoplastic Protein Biosynthesis Ribosomes 030217 neurology & neurosurgery |
Zdroj: | Nucleic Acids Research Nucleic Acids Research, 48(13), 7079-7098. Oxford University Press |
ISSN: | 0305-1048 |
Popis: | 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. |
Databáze: | OpenAIRE |
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