{"doi":"10.1016/j.molcel.2023.12.003","title":"Translation of non-canonical open reading frames as a cancer cell survival mechanism in childhood medulloblastoma","abstract":"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 (ORFs). 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 stepwise 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 ORFs (uORFs) exhibited selective functionality independent of main coding sequences. A microprotein encoded by one of these ORFs, ASNSD1-uORF or ASDURF, was upregulated, associated with MYC-family oncogenes, and promoted 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.","journal":"Molecular Cell","year":2024,"id":417470,"datarank":1.4667320914789455,"base_score":4.248495242049359,"endowment":4.248495242049359,"self_citation_contribution":0.637274286307404,"citation_network_contribution":0.8294578051715414,"self_endowment_contribution":0.637274286307404,"citer_contribution":0.8294578051715414,"corpus_percentile":null,"corpus_rank":null,"citation_count":69,"citer_count":57,"citers_with_citation_signal":39,"citers_with_endowment":39,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":17867,"name":"Jorge Ruiz-Orera","orcid":"0000-0002-8317-0034","position":1,"is_corresponding":false},{"id":778149,"name":"Ian Yannuzzi","orcid":"0000-0002-0216-4805","position":2,"is_corresponding":false},{"id":1163248,"name":"Rakesh Murugesan","orcid":"0000-0003-1716-2615","position":3,"is_corresponding":false},{"id":253762,"name":"Adam Brown","orcid":"0000-0002-9122-4960","position":4,"is_corresponding":false},{"id":2216,"name":"Karl R. 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