Regulation of translation by methylation multiplicity of 18S rRNA
Kuanqing Liu,
Daniel A. Santos,
Jeffrey A. Hussmann,
Yun Wang,
Benjamin M. Sutter,
Jonathan S. Weissman,
Benjamin P. Tu
Affiliations
Kuanqing Liu
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA
Daniel A. Santos
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA
Jeffrey A. Hussmann
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA
Yun Wang
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA
Benjamin M. Sutter
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA
Jonathan S. Weissman
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA
Benjamin P. Tu
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA; Corresponding author
Summary: N6-methyladenosine (m6A) is a conserved ribonucleoside modification that regulates many facets of RNA metabolism. Using quantitative mass spectrometry, we find that the universally conserved tandem adenosines at the 3′ end of 18S rRNA, thought to be constitutively di-methylated (m62A), are also mono-methylated (m6A). Although present at substoichiometric amounts, m6A at these positions increases significantly in response to sulfur starvation in yeast cells and mammalian cell lines. Combining yeast genetics and ribosome profiling, we provide evidence to suggest that m6A-bearing ribosomes carry out translation distinctly from m62A-bearing ribosomes, featuring a striking specificity for sulfur metabolism genes. Our work thus reveals methylation multiplicity as a mechanism to regulate translation.
