Regulation of translation by site-specific ribosomal RNA methylation

Martin David Jansson, Sophia Julia Häfner, Kübra Altinel, Disa Elisabet Tehler, Nicolai Krogh, Emil Jakobsen, Jens Velde Andersen, Kasper Langebjerg Andersen, Erwin Schoof, Patrice Ménard, Henrik Nielsen, Anders H. Lund*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Abstract

Ribosomes are complex ribozymes that interpret genetic information by translating messenger RNA (mRNA) into proteins. Natural variation in ribosome composition has been documented in several organisms and can arise from several different sources. A key question is whether specific control over ribosome heterogeneity represents a mechanism by which translation can be regulated. We used RiboMeth-seq to demonstrate that differential 2′-O-methylation of ribosomal RNA (rRNA) repre- sents a considerable source of ribosome heterogeneity in human cells, and that modification levels at distinct sites can change dynamically in response to upstream signaling pathways, such as MYC oncogene expression. Ablation of one prominent meth- ylation resulted in altered translation of select mRNAs and corresponding changes in cellular phenotypes. Thus, differential rRNA 2′-O-methylation can give rise to ribosomes with specialized function. This suggests a broader mechanism where the specific regulation of rRNA modification patterns fine tunes translation.
OriginalsprogEngelsk
TidsskriftNature Structural and Molecular Biology
Vol/bind28
Udgave nummer11
Sider (fra-til)889-899
ISSN1545-9993
DOI
StatusUdgivet - 2021

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