A novel splice variant of Elp3/Kat9 regulates mitochondrial tRNA modification and function

Post-translational modifications, such as lysine acetylation, regulate the activity of diverse proteins across many cellular compartments. Protein deacetylation in mitochondria is catalyzed by the enzymatic activity of the NAD + -dependent deacetylase sirtuin 3 (SIRT3), however it remains unclear wh...

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Bibliographic Details
Published in:Scientific reports Vol. 12; no. 1; pp. 14804 - 14
Main Authors: Boutoual, Rachid, Jo, Hyunsun, Heckenbach, Indra, Tiwari, Ritesh, Kasler, Herbert, Lerner, Chad A., Shah, Samah, Schilling, Birgit, Calvanese, Vincenzo, Rardin, Matthew J., Scheibye-Knudsen, Morten, Verdin, Eric
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 31.08.2022
Nature Publishing Group
Nature Portfolio
Subjects:
631/208
631/337
631/80
Acetylation
Acetyltransferase
Alternative splicing
Angiogenin
Bioinformatics
Deacetylation
Enzymatic activity
Enzymes
Genomes
Humanities and Social Sciences
Localization
Lysine
Mammalian cells
Mass spectrometry
Metabolism
Mitochondria
multidisciplinary
Post-transcription
Post-translation
Proteins
Ribonuclease
Science
Science (multidisciplinary)
Scientific imaging
Transfer RNA
tRNA
tRNA Ala
ISSN:2045-2322, 2045-2322
Online Access:Get full text
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Summary:Post-translational modifications, such as lysine acetylation, regulate the activity of diverse proteins across many cellular compartments. Protein deacetylation in mitochondria is catalyzed by the enzymatic activity of the NAD + -dependent deacetylase sirtuin 3 (SIRT3), however it remains unclear whether corresponding mitochondrial acetyltransferases exist. We used a bioinformatics approach to search for mitochondrial proteins with an acetyltransferase catalytic domain, and identified a novel splice variant of ELP3 (mt-ELP3) of the elongator complex, which localizes to the mitochondrial matrix in mammalian cells. Unexpectedly, mt-ELP3 does not mediate mitochondrial protein acetylation but instead induces a post-transcriptional modification of mitochondrial-transfer RNAs (mt-tRNAs). Overexpression of mt-ELP3 leads to the protection of mt-tRNAs against the tRNA-specific RNase angiogenin, increases mitochondrial translation, and furthermore increases expression of OXPHOS complexes. This study thus identifies mt-ELP3 as a non-canonical mt-tRNA modifying enzyme.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-18114-x