PXD046091

PXD046091 is an original dataset announced via ProteomeXchange.

Title	Human medulloblastoma ASNSD1 uORF KO LC-MSMS
Description	A hallmark of high-risk childhood medulloblastoma is the dysregulation of RNA translation. Currently, it is unknown whether medulloblastoma dysregulates the translation of putatively oncogenic non-canonical open reading frames. To address this question, we performed ribosome profiling of 32 medulloblastoma tissues and cell lines and observed widespread non-canonical ORF translation. We then developed a step-wise approach using multiple CRISPR-Cas9 screens to elucidate non-canonical ORFs and putative microproteins implicated in medulloblastoma cell survival. We determined that multiple lncRNA-ORFs and upstream open reading frames (uORFs) exhibited selective functionality independent of the main coding sequence. A microprotein encoded by one of these ORFs, ASNSD1-uORF or ASDURF, was upregulated, associated with the MYC family oncogenes, and was required for medulloblastoma cell survival through engagement with the prefoldin-like chaperone complex. Our findings underscore the fundamental importance of non-canonical ORF translation in medulloblastoma and provide a rationale to include these ORFs in future studies seeking to define new cancer targets.
HostingRepository	PRIDE
AnnounceDate	2024-01-04
AnnouncementXML	Submission_2024-01-04_05:58:58.744.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Damon Hofman
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-12 08:36:43	ID requested
⏵ 1	2024-01-04 05:58:59	announced

10.1101/2023.05.04.539399;

10.1016/J.MOLCEL.2023.12.003;

Hofman DA, Ruiz-Orera J, Yannuzzi I, Murugesan R, Brown A, Clauser KR, Condurat AL, van Dinter JT, Engels SAG, Goodale A, van der Lugt J, Abid T, Wang L, Zhou KN, Vogelzang J, Ligon KL, Phoenix TN, Roth JA, Root DE, Hubner N, Golub TR, Bandopadhayay P, van Heesch S, Prensner JR, Translation of non-canonical open reading frames as a cancer cell survival mechanism in childhood medulloblastoma. bioRxiv, ():(2023) [pubmed]

submitter keyword: Human, LC-MSMS, medulloblastoma, knockout

John R. Prensner
contact affiliation	Department of Pediatrics, Division of Pediatric Hematology/Oncology and Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA
contact email	prensner@umich.edu
lab head
Damon Hofman
contact affiliation	Princess Maxima Center for Pediatric Oncology
contact email	d.a.hofman-3@prinsesmaximacentrum.nl
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/2024/01/PXD046091

PRIDE project URI

• PRIDE
  1. PXD046091
     1. Label: PRIDE project
     2. Name: Human medulloblastoma ASNSD1 uORF KO LC-MSMS