1. Regulation of translation by site-specific ribosomal RNA methylation
- Author
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Anders H. Lund, Sophia Häfner, Disa Tehler, Martin D. Jansson, Erwin M. Schoof, Nicolai Krogh, Patrice Menard, Henrik Nielsen, Emil Jakobsen, Kübra Altinel, Kasper L. Andersen, and Jens V. Andersen
- Subjects
Messenger RNA ,Ribozyme ,Translation (biology) ,Methylation ,Biology ,Ribosomal RNA ,Ribosome ,Cell biology ,Proto-Oncogene Proteins c-myc ,RRNA modification ,RNA, Ribosomal ,Structural Biology ,Cell Line, Tumor ,Protein Biosynthesis ,biology.protein ,Humans ,RNA, Messenger ,RNA Processing, Post-Transcriptional ,Protein Processing, Post-Translational ,Ribosomes ,Molecular Biology ,Function (biology) ,HeLa Cells - 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. 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.
- Published
- 2021