PXD030418

PXD030418 is an original dataset announced via ProteomeXchange.

Title	METTL8 is required for 3-methylcytosine modification in human mitochondrial tRNAs
Description	A subset of eukaryotic tRNAs is methylated in the anticodon loop to form the 3-methylcytosine (m3C) modification. In mammals, the number of tRNAs containing m3C has expanded to include mitochondrial (mt) tRNA-Ser-UGA and mt-tRNA-Thr-UGU. Whereas the enzymes catalyzing m3C formation in nuclear-encoded cytoplasmic tRNAs have been identified, the proteins responsible for m3C modification in mt-tRNAs are unknown. Here, we show that m3C formation in human mt-tRNAs is dependent upon the Methyltransferase-Like 8 (METTL8) enzyme. We find that METTL8 is a mitochondria-associated protein that interacts with mitochondrial seryl-tRNA synthetase along with mt-tRNAs containing m3C. Human cells deficient in METTL8 exhibit loss of m3C modification in mt-tRNAs but not nuclear-encoded tRNAs. Consistent with the mitochondrial import of METTL8, the formation of m3C in METTL8-deficient cells can be rescued by re-expression of wildtype METTL8 but not by a METTL8 variant lacking the N-terminal mitochondrial localization signal. Notably, METTL8-deficiency in human cells causes alterations in the native migration pattern of mt-tRNA-Ser-UGA suggesting a role for m3C in tRNA folding. Altogether, these findings demonstrate that METTL8 is required for m3C formation in mitochondrial tRNAs and uncover a potential role for m3C modification in mitochondrial tRNA structure.
HostingRepository	PRIDE
AnnounceDate	2022-05-19
AnnouncementXML	Submission_2022-05-19_09:23:41.172.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kyle Swovick
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-15 04:44:14	ID requested
⏵ 1	2022-05-19 09:23:41	announced

Lentini JM, Bargabos R, Chen C, Fu D, Methyltransferase METTL8 is required for 3-methylcytosine modification in human mitochondrial tRNAs. J Biol Chem, 298(4):101788(2022) [pubmed]

submitter keyword: METTL8, tRNA, tRNA modification, 3-methylcytosine, m3C, mitochondria

Dragony Fu
contact affiliation	Department of Biology, Center for RNA Biology, University of Rochester, Rochester, New York, United States of America
contact email	dragonyfu@rochester.edu
lab head
Kyle Swovick
contact affiliation	University of Rochester Medical Center Mass Spectrometry Shared Resource Laboratory
contact email	kswovick@ur.rochester.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/05/PXD030418

PRIDE project URI

• PRIDE
  1. PXD030418
     1. Label: PRIDE project
     2. Name: METTL8 is required for 3-methylcytosine modification in human mitochondrial tRNAs