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

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Funding Agencies|Tri-Institutional Stem Cell Initiative by the Starr Foundation; NIH [GM079238]; Jacques Cohenca Predoctoral Fellowship
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 ribosomes 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 5S, 5.8S, 18S, and 28S 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.

Kurylo, Chad M.Weill Cornell Med, NY 10065 USA (författare)
Dass, Randall A.Weill Cornell Med, NY 10065 USA (författare)
Bojmar, LindaLinköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Weill Cornell Med, NY 10065 USA; Karolinska Inst, Sweden(Swepub:liu)linbo68 (författare)
Lyden, DavidWeill Cornell Med, NY 10065 USA; Mem Sloan Kettering Canc Ctr, NY 10065 USA (författare)
Vincent, C. TheresaKarolinska Institutet,Weill Cornell Med, NY 10065 USA; Karolinska Inst, Sweden (författare)
Blanchard, Scott C.Weill Cornell Med, NY 10065 USA (författare)
Weill Cornell Med, NY 10065 USAAvdelningen för Kirurgi, Ortopedi och Onkologi (creator_code:org_t)

Av författaren/redakt...: Parks, Matthew M ...; Kurylo, Chad M.; Dass, Randall A.; Bojmar, Linda; Lyden, David; Vincent, C. Ther ...; visa fler...; Blanchard, Scott ...; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Cell och molekyl ...

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