MRM2 encodes a novel yeast mitochondrial 21S rRNA methyltransferase

Abstract

Mitochondria of the yeast Saccharomyces cerevisiae assemble their ribosomes from ribosomal proteins, encoded by the nuclear genome (with one exception), and rRNAs of 15S and 21S, encoded by the mitochondrial genome. Unlike cytoplasmic rRNA, which is highly modi®ed, mitochondrial rRNA contains only three modi®ed nucleotides: a pseudouridine (Y 2918 ) and two 2¢-O-methylated riboses (Gm 2270 and Um 2791 ) located at the peptidyl transferase centre of 21S rRNA. We demonstrate here that the yeast nuclear genome encodes a mitochondrial protein, named Mrm2, which is required for methylating U 2791 of 21S rRNA, both in vivo and in vitro. Deletion of the MRM2 gene causes thermosensitive respiration and leads to rapid loss of mitochondrial DNA. We propose that Mrm2p belongs to a new class of three eukaryotic RNA-modifying enzymes and is the orthologue of FtsJ/RrmJ, which methylates a nucleotide of the peptidyl transferase centre of Escherichia coli 23S rRNA that is homologous to U 2791 of 21S rRNA. Our data suggest that this universally conserved modi®ed nucleotide plays an important function in vivo, possibly by inducing conformational rearrangement of the peptidyl transferase centre.

Mitochondrial Ribosomal RNA (rRNA) Methyltransferase Family Members Are Positioned to Modify Nascent rRNA in Foci near the Mitochondrial DNA Nucleoid

“…that they may act not on free 16 S rRNA but on RNA-protein complexes that are intermediates in ribosome assembly, as is the case for yeast MRM2 (18). Additional experiments beyond the scope of our present work will be required to confirm and characterize the activity of these methyltransferase family members.…”

“…In keeping with their prokaryotic ancestry, yeast mitochondria employ individual enzymes for rRNA methylation. In yeast, 2Ј-O-ribose modification by Pet56p generates Gm 2270 , whereas Mrm2p generates Um 2791 (17,18). Although these modifications are separated by over 500 nucleotides in the primary sequence, they both fold into the peptidyltransferase center of the mitochondrial ribosome (38).…”

“…These sites are conserved in bacterial and cytoplasmic rRNAs, where they stabilize RNA structures critical for the peptidyltransferase reaction and tRNA recognition (5). These modifications have been studied in yeast rRNA, where methylation of the residue homologous to human G 1145 has been attributed to MRM1/PET56 (17), and that analogous to U 1369 methylation is conducted by MRM2 (18). Yeast rRNA evidently lacks the G 1370 methylation.…”

MidA is a putative methyltransferase that is required for mitochondrial complex I function

“…In mitochondria, methylation has an essential role. Mitochondrial DNA, tRNA and rRNA are all targets of specific methylation events (Helm et al, 1998;Pintard et al, 2002) and specific carriers transport SAM into the mitochondria (Agrimi et al, 2004). As far as protein methylation is concerned, only two methylated subunits have been detected in complex I subunits.…”

Alcohol-induced S-adenosylhomocysteine accumulation in the liver sensitizes to TNF hepatotoxicity: Possible involvement of mitochondrial S-adenosylmethionine transport

“…In addition to the synthesis of phospholipids, SAM is essential for the methylation of various types of nucleic acids present in the mitochondria. In mammals, methylation of DNA, tRNA and rRNA has been documented, and some have been shown to be essential for mitochondrial function [44][45][46][47]. SAM is also necessary for post-translational modifications of some mitochondrial proteins.…”