title: Mitochondrial 16S rRNA Is Methylated by tRNA Methyltransferase TRMT61B in All Vertebrates.
abstract: The mitochondrial ribosome, which translates all mitochondrial DNA (mtDNA)-encoded proteins, should be tightly regulated pre- and post-transcriptionally. Recently, we found RNA-DNA differences (RDDs) at human mitochondrial 16S (large) rRNA position 947 that were indicative of post-transcriptional modification. Here, we show that these 16S rRNA RDDs result from a 1-methyladenosine (m1A) modification introduced by TRMT61B, thus being the first vertebrate methyltransferase that modifies both tRNA and rRNAs. m1A947 is conserved in humans and all vertebrates having adenine at the corresponding mtDNA position (90% of vertebrates). However, this mtDNA base is a thymine in 10% of the vertebrates and a guanine in the 23S rRNA of 95% of bacteria, suggesting alternative evolutionary solutions. m1A, uridine, or guanine may stabilize the local structure of mitochondrial and bacterial ribosomes. Experimental assessment of genome-edited Escherichia coli showed that unmodified adenine caused impaired protein synthesis and growth. Our findings revealed a conserved mechanism of rRNA modification that has been selected instead of DNA mutations to enable proper mitochondrial ribosome function.
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Bar-Yaacov
authors.affiliation: Department of Molecular Genetics, the Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Idan
authors.initials: I
authors.lastname: Frumkin
authors.affiliation: Department of Chemistry and Biotechnology, University of Tokyo, Tokyo, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yashiro
authors.affiliation: Department of Chemistry and Biotechnology, University of Tokyo, Tokyo, Japan.
authors.forename: Takeshi
authors.identifier: 0000-0003-2393-5776
authors.initials: T
authors.lastname: Chujo
authors.affiliation: Department of Chemistry and Biotechnology, University of Tokyo, Tokyo, Japan.
authors.forename: Yuma
authors.identifier: 0000-0002-5704-291X
authors.initials: Y
authors.lastname: Ishigami
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.|The Ilse Katz Institute for Nanoscale Science and Technology, Beer Sheva, Israel.
authors.forename: Yonatan
authors.identifier: 0000-0002-0465-9393
authors.initials: Y
authors.lastname: Chemla
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Amit
authors.identifier: 0000-0001-5257-3722
authors.initials: A
authors.lastname: Blumberg
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.|The Ilse Katz Institute for Nanoscale Science and Technology, Beer Sheva, Israel.
authors.forename: Orr
authors.initials: O
authors.lastname: Schlesinger
authors.affiliation: Department of Biology, Institute of Molecular Biology and Biophysics, Zurich, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Bieri
authors.affiliation: Department of Biology, Institute of Molecular Biology and Biophysics, Zurich, Switzerland.
authors.forename: Basil
authors.initials: B
authors.lastname: Greber
authors.affiliation: Department of Biology, Institute of Molecular Biology and Biophysics, Zurich, Switzerland.
authors.forename: Nenad
authors.initials: N
authors.lastname: Ban
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Raz
authors.initials: R
authors.lastname: Zarivach
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.|The Ilse Katz Institute for Nanoscale Science and Technology, Beer Sheva, Israel.
authors.forename: Lital
authors.initials: L
authors.lastname: Alfonta
authors.affiliation: Department of Molecular Genetics, the Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yitzhak
authors.initials: Y
authors.lastname: Pilpel
authors.affiliation: Department of Chemistry and Biotechnology, University of Tokyo, Tokyo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Mishmar
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D004926:Escherichia coli; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D008928:Mitochondria / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism; D000077278:RNA, Mitochondrial; D012336:RNA, Ribosomal, 16S / Q000235:genetics / Q000378:metabolism*; D012359:tRNA Methyltransferases / Q000502:physiology*
chemical_list: D012329:RNA, Bacterial; D000077278:RNA, Mitochondrial; D012336:RNA, Ribosomal, 16S; C002230:1-methyladenosine; D012313:RNA; C577855:Trmt61B protein, human; D012359:tRNA Methyltransferases; D000241:Adenosine