TY - JOUR
T1 - Regulation of translation by site-specific ribosomal RNA methylation
AU - Jansson, Martin David
AU - Häfner, Sophia Julia
AU - Altinel, Kübra
AU - Tehler, Disa Elisabet
AU - Krogh, Nicolai
AU - Jakobsen, Emil
AU - Andersen, Jens Velde
AU - Andersen, Kasper Langebjerg
AU - Schoof, Erwin
AU - Ménard, Patrice
AU - Nielsen, Henrik
AU - Lund, Anders H.
PY - 2021
Y1 - 2021
N2 - 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) represents 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 methylation 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.
AB - 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) represents 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 methylation 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.
U2 - 10.1038/s41594-021-00669-4
DO - 10.1038/s41594-021-00669-4
M3 - Journal article
C2 - 34759377
VL - 28
SP - 889
EP - 899
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
SN - 1545-9993
IS - 11
ER -