A novel splice variant of Elp3/Kat9 regulates mitochondrial tRNA modification and function
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A novel splice variant of Elp3/Kat9 regulates mitochondrial tRNA modification and function. / 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.
In: Scientific Reports, Vol. 12, 14804, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A novel splice variant of Elp3/Kat9 regulates mitochondrial tRNA modification and function
AU - Boutoual, Rachid
AU - Jo, Hyunsun
AU - Heckenbach, Indra
AU - Tiwari, Ritesh
AU - Kasler, Herbert
AU - Lerner, Chad A.
AU - Shah, Samah
AU - Schilling, Birgit
AU - Calvanese, Vincenzo
AU - Rardin, Matthew J.
AU - Scheibye-Knudsen, Morten
AU - Verdin, Eric
N1 - Publisher Copyright: © 2022. The Author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-022-18114-x
DO - 10.1038/s41598-022-18114-x
M3 - Journal article
C2 - 36045139
AN - SCOPUS:85137042599
VL - 12
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 14804
ER -
ID: 319398455