Mishmar 2015 Abstract MiP2015

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Mitochondrial 16S rRNA is methylated (m1A) throughout vertebrate evolution to maintain protein synthesis and cell growth.

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Bar-Yaacov D, Frumkin I, Chemla Y, Blumberg A, Schlesinger O, Bieri P, Greber B, Ban N, Zarivach R, Alfonta L, Pilpel Y, Suzuki T, Mishmar D (2015)

Event: MiP2015

Canonical RNA-DNA-Differences (RDDs), i.e. A-to-G and C-to-U, are important for mammalian sequence diversity. However, non-canonical RDDs have been questioned. Recently, we identified both canonical and non-canonical RDDs (A-to-U and A-to-G) in human mitochondrial 16S rRNA position 947, and suggested that they echo RNA modification. Here, using mass spectrometry and primer extension of 16S rRNA transcripts in human TRMT61B-silenced cells, we show that the RDDs reflect a 1-methyladenosine (m1A) modification. Since these 16S rRNA RDDs were found in all tested human mitochondrial genomes (mtDNAs, ~10,000) and tissues, as well as in 90% of all available vertebrates (N>1700), the m1A modification is likely important. Moreover, the m1A alters a bacteria-to-human structurally conserved interface between the small and large mitoribosomal subunits. However, this mtDNA base is a thymine in 10% of the vertebrates, and guanine in most (95%) bacteria (N>1300), suggesting functional evolutionary alternatives. Since human mtDNA cannot be modified in vivo, we tested this hypothesis in mutant Escherichia coli. Strikingly, bacterial strains with the mtDNA base (adenine) had impaired protein synthesis and growth as compared to strains with a thymine or a guanine. Modeling m1A, thymine or guanine in the mitoribosome, demonstrated stabilized structure, in contrast to the mtDNA base (adenine). Hence, either 16S rRNA m1A modification, or thymine or guanine in the DNA, are evolutionary alternatives that stabilize mitoribosomes for proper mitochondrial translation. Furthermore, our findings offer a testable model for the occurrence of non-canonical RDDs throughout the human genome.


Labels: MiParea: Instruments;methods, mtDNA;mt-genetics, Comparative MiP;environmental MiP 


Organism: Human, Eubacteria 




Event: C1, Oral  MiP2015 

Affiliations

1-Dept Life Sc, Ben-Gurion Univ Negev, Beer Sheva, Israel; 2-Dept Mol Genet, Weizmann Inst Science, Rehovot, Israel; 3-Ilse Katz Inst Nanoscale Sc Technology, Beer Sheva, Israel; 4-Dept Biol, Inst Mol Biol Biophysics, ETH Zurich, Switzerland; 5-Dept Chem Biotechn, Univ Tokyo, Bunkyo-ku, Tokyo, Japan. - dmishmar@bgu.ac.il