Mitochondrial 16S rRNA Is Methylated by tRNA Methyltransferase TRMT61B in All Vertebrates

Dan Bar-Yaacov, Idan Frumkin, Yuka Yashiro, Takeshi Chujo, Yuma Ishigami, Yonatan Chemla, Amit Blumberg, Orr Schlesinger, Philipp Bieri, Basil Greber, Nenad Ban, Raz Zarivach, Lital Alfonta, Yitzhak Pilpel, Tsutomu Suzuki, Dan Mishmar

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

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.

Original languageEnglish
Article numbere1002557
JournalPLoS Biology
Volume14
Issue number9
DOIs
StatePublished - 15 Sep 2016

Keywords

  • Adenosine/analogs & derivatives
  • Animals
  • Escherichia coli
  • HeLa Cells
  • Humans
  • Methylation
  • Mitochondria/genetics
  • RNA/genetics
  • RNA Processing, Post-Transcriptional
  • RNA, Bacterial/genetics
  • RNA, Mitochondrial
  • RNA, Ribosomal, 16S/genetics
  • tRNA Methyltransferases/physiology

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