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

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.

Human/eukaryotic ribosomal protein L14 (RPL14/eL14) overexpression represses proliferation, migration, invasion and EMT process in nasopharyngeal carcinoma

“…In addition, Feng et al found that RPL14(eL14) promoted cancer invasion and migration in cervical cancer [12]. All these data not only indicated that the expression of RPL14(eL14) may have specific tissue heterogeneity [31,32] but also effectively confirm that RPL14(eL14) may serve as an important regulator in tumor progression.…”

Quantitative ubiquitylomics reveals the ubiquitination regulation landscape in oral adenoid cystic carcinoma

“…Ribosomal proteins are abnormally expressed in a variety of tumors, which affect the apoptosis, aging, growth, invasion, drug and radiation resistance [75]. The expression level of ribosomal protein has become a potential indicator of tumor diagnosis, treatment and prognosis [76]. Bioscience Reports.…”

“…Ribosomal proteins are abnormally expressed in a variety of tumors, which affect the apoptosis, aging, growth, invasion, drug and radiation resistance [ 75 ]. The expression level of ribosomal protein has become a potential indicator of tumor diagnosis, treatment and prognosis [ 76 ]. Through the in-depth study of abnormal expression and ubiquitination modification of ribosomal proteins in tumor tissue, we can further understand the role of high expression of ribosomal protein gene in malignant tumor.…”

Are there roles for heterogeneous ribosomes during sleep in the rodent brain?

“…Ribosomopathies are pathologies which result from mutations in certain RP genes ( Orgebin et al, 2020 ), with as many as 20 RP genes, including RPS19, involved in Diamond-Blackfan anaemia (DBA) ( Leger-Silvestre et al, 2005 ; Da Costa et al, 2020 ). Besides a deficiency of erythroblasts, about 50% of DBA patients experience other congenital anomalies such as growth retardation, cardiac and urogenital abnormalities, increased risk of cancer, cephalic malformations and learning difficulties ( Da Costa et al, 2020 ; Panda et al, 2020 ). Fragile-X syndrome is another well-characterised neurodevelopmental disorder associated with intellectual disability and learning difficulties.…”