PXD036538-1

PXD036538 is an original dataset announced via ProteomeXchange.

Title	Human TRMT2A methylates different components of the translation machinery and contributes to translation fidelity
Description	Methyl-5-uridine (m5U) is one of the most abundant RNA modifications found in cytosolic tRNA. tRNA methyltransferase 2 homolog A (hTRMT2A) is the dedicated mammalian enzyme of m5U conversion at tRNA position 54. However, its RNA binding specificity and functional role in the cell are not well understood. Here we dissected structural and sequence requirements for binding and methylation of its RNA targets. Specificity of tRNA modification by TRMT2A is achieved by a combination of modest binding preference and presence of a uridine in position 54 of tRNAs. Mutational analysis together with crosslinking experiments identified a large hTRMT2A-tRNA binding surface. Furthermore, complementing hTRMT2A interactome studies revealed that TRMT2A interacts with proteins involved in both tRNA and rRNA biogenesis. Consistent with this finding, we observed that TRMT2A not only methylates tRNA, but also rRNA. Finally, we addressed the question of the importance of TRMT2A function by showing that its knockdown reduces translational fidelity. These findings extend the role of hTRMT2A beyond tRNA modification towards rRNA biogenesis and translational fidelity.
HostingRepository	PRIDE
AnnounceDate	2023-07-04
AnnouncementXML	Submission_2023-07-04_04:01:27.129.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	StefanieHauck
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-05 10:00:55	ID requested
⏵ 1	2023-07-04 04:01:27	announced
2	2023-11-14 09:02:10	announced	2023-11-14: Updated project metadata.

Witzenberger M, Burczyk S, Settele D, Mayer W, Welp LM, Heiss M, Wagner M, Monecke T, Janowski R, Carell T, Urlaub H, Hauck SM, Voigt A, Niessing D, Human TRMT2A methylates tRNA and contributes to translation fidelity. Nucleic Acids Res, 51(16):8691-8710(2023) [pubmed]

submitter keyword: RNA biogenesis, translational fidelity,Methyl-5-uridine (m5U), RNA methylation, tRNA methyltransferase 2 homolog A (hTRMT2A), interactome, mammalia

Stefanie M.Hauck
contact affiliation	Metabolomics and Proteomics Core, Helmholtz Zentrum München, German Center for Environmental Health
contact email	hauck@helmholtz-muenchen.de
lab head
StefanieHauck
contact affiliation	Research Unit Protein Science, Helmholtz Zentrum München
contact email	hauck@helmholtz-muenchen.de
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/2023/07/PXD036538

PRIDE project URI

• PRIDE
  1. PXD036538
     1. Label: PRIDE project
     2. Name: Human TRMT2A methylates different components of the translation machinery and contributes to translation fidelity