PXD030141-3

PXD030141 is an original dataset announced via ProteomeXchange.

Title	Guanosine-7 tRNA methylation steers tRNA-derived fragment biogenesis and translational control in prostate cancer
Description	Transfer RNAs (tRNAs) are exceptionally subject to modifications, including methylation. While mRNA methylation is emerging as an important regulator of biological and pathological processes in cancer, how post-transcriptional methylation of tRNAs contributes to cancer is largely unknown. Here we show that the RNA N7-methylguanosine (m7G) methyltransferase METTL1 is highly differentially expressed in prostate cancer compared to non-tumour prostate tissues. METTL1 expression regulation is mediated under the oncogenic PI3K-PTEN pathway. Knockdown of METTL1 dramatically inhibits prostate cancer cell growth and tumour progression in vivo. In contrast, overexpression of the wild type but not the catalytically inactive METTL1 potentiates cell growth. Thus, METTL1-mediated methylation is important for prostate tumorigenesis. Mechanistically we find that METTL1 depletion causes loss of m7G tRNA methylation and increases endonucleolytic cleavage of tRNA leading to an accumulation of 5′ tRNA-derived small RNA fragments. 5′ tRNA-derived fragments steer translation control to favour synthesis of key regulators of tumour growth suppression and immune rejection. In summary, our findings uncover a critical function of m7G tRNA methylation in directing translation control in cancer cells with important implications for tumour growth and unveil METTL1 inhibition as a promising anti-cancer therapeutic strategy.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:09:30.616.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mikel Azkargorta
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-02 08:27:07	ID requested
1	2023-10-24 12:08:27	announced
2	2023-11-14 09:08:41	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 06:09:31	announced	2024-10-22: Updated project metadata.

10.1186/s12943-023-01809-8;

Garc, í, a-V, í, lchez R, A, ñ, azco-Guenkova AM, Dietmann S, L, ó, pez J, Mor, ó, n-Calvente V, D'Ambrosi S, Nombela P, Zamacola K, Mendizabal I, Garc, í, a-Longarte S, Zabala-Letona A, Astobiza I, Fern, á, ndez S, Paniagua A, Miguel-L, ó, pez B, Marchand V, Alonso-L, ó, pez D, Merkel A, Garc, í, a-Tu, ñ, ó, n I, Ugalde-Olano A, Loizaga-Iriarte A, Lacasa-Viscasillas I, Unda M, Azkargorta M, Elortza F, B, á, rcena L, Gonzalez-Lopez M, Aransay AM, Di Domenico T, S, á, nchez-Mart, í, n MA, De Las Rivas J, Guil S, Motorin Y, Helm M, Pandolfi PP, Carracedo A, Blanco S, METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer. Mol Cancer, 22(1):119(2023) [pubmed]

submitter keyword: cancer, RNA modifications, 7-methylguanosine, prostate cancer, tRNAs, tRNA fragments,Epitranscriptome, protein synthesis, translatome

Felix Elortza
contact affiliation	Proteomics Platform CIC bioGUNE, Bizkaia Tec. Park Build. 800, derio 48160 Bizkaia (Spain)
contact email	felortza@cicbiogune.es
lab head
Mikel Azkargorta
contact affiliation	Proteomics Platform CIC bioGUNE
contact email	mazkargorta@cicbiogune.es
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/2023/10/PXD030141

PRIDE project URI

• PRIDE
  1. PXD030141
     1. Label: PRIDE project
     2. Name: Guanosine-7 tRNA methylation steers tRNA-derived fragment biogenesis and translational control in prostate cancer