Variant ribosomal RNA alleles are conserved and exhibit tissue-specific expression

The ribosome, the integration point for protein synthesis in the cell, is conventionally considered a homogeneous molecular assembly that only passively contributes to gene expression. Yet, epigenetic features of the ribosomal DNA (rDNA) operon and changes in the ribosome's molecular compositio...

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Bibliographic Details
Published in:Science advances 2018-02, Vol.4 (2), p.eaao0665-eaao0665
Main Authors: Parks, Matthew M, Kurylo, Chad M, Dass, Randall A, Bojmar, Linda, Lyden, David, Vincent, C Theresa, Blanchard, Scott C
Format: Article
Language:English
Subjects:
Alleles
Animals
Base Sequence
Chromosomes, Human - genetics
Conserved Sequence - genetics
DNA, Ribosomal - genetics
Evolution, Molecular
Gene Dosage
Gene Expression Profiling
Gene Expression Regulation
Genetics
Genome, Human
HEK293 Cells
Humans
Medicin och hälsovetenskap
Mice
Mutation - genetics
Operon - genetics
Organ Specificity - genetics
Protein Biosynthesis
Protein Subunits - genetics
Ribosomes - metabolism
RNA Processing, Post-Transcriptional - genetics
RNA, Ribosomal - genetics
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Summary:The ribosome, the integration point for protein synthesis in the cell, is conventionally considered a homogeneous molecular assembly that only passively contributes to gene expression. Yet, epigenetic features of the ribosomal DNA (rDNA) operon and changes in the ribosome's molecular composition have been associated with disease phenotypes, suggesting that the ribosome itself may possess inherent regulatory capacity. Analyzing whole-genome sequencing data from the 1000 Genomes Project and the Mouse Genomes Project, we find that rDNA copy number varies widely across individuals, and we identify pervasive intra- and interindividual nucleotide variation in the 5 , 5.8 , 18 , and 28 ribosomal RNA (rRNA) genes of both human and mouse. Conserved rRNA sequence heterogeneities map to functional centers of the assembled ribosome, variant rRNA alleles exhibit tissue-specific expression, and ribosomes bearing variant rRNA alleles are present in the actively translating ribosome pool. These findings provide a critical framework for exploring the possibility that the expression of genomically encoded variant rRNA alleles gives rise to physically and functionally heterogeneous ribosomes that contribute to mammalian physiology and human disease.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.aao0665