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

TitleVariant ribosomal RNA alleles are conserved and exhibit tissue-specific expression.
Publication TypeJournal Article
Year of Publication2018
AuthorsParks MM, Kurylo CM, Dass RA, Bojmar L, Lyden DC, C Vincent T, Blanchard SC
JournalSci Adv
Date Published2018 02
KeywordsAlleles, Animals, Base Sequence, Chromosomes, Human, Conserved Sequence, DNA, Ribosomal, Evolution, Molecular, Gene Dosage, Gene Expression Profiling, Gene Expression Regulation, Genome, Human, HEK293 Cells, Humans, Mice, Mutation, Operon, Organ Specificity, Protein Biosynthesis, Protein Subunits, Ribosomes, RNA Processing, Post-Transcriptional, RNA, Ribosomal

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.

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Alternate JournalSci Adv
PubMed ID29503865
PubMed Central IDPMC5829973
Grant ListR01 GM079238 / GM / NIGMS NIH HHS / United States

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