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

PLoS Biol. 2016 Sep 15;14(9):e1002557. doi: 10.1371/journal.pbio.1002557. eCollection 2016 Sep.

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.

MeSH terms

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

Substances

  • RNA, Bacterial
  • RNA, Mitochondrial
  • RNA, Ribosomal, 16S
  • 1-methyladenosine
  • RNA
  • Trmt61B protein, human
  • tRNA Methyltransferases
  • Adenosine

Grant support

This work was supported by research grants from the Israeli Science Foundation (610-12) and Binational Science Foundation (2013060) awarded to DM. DBY and YC are both supported by a Negev scholarship for distinguished PhD students, AB is supported by the Harbor Foundation scholarship for excellent PhD students, and IF is supported by the Azrieli Foundation scholarship for distinguished PhD students. The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.