Damon A Hofman, Jorge Ruiz-Orera, Ian Yannuzzi, Rakesh Murugesan, Adam Brown, Karl R Clauser, Alexandra L Condurat, Jip T van Dinter, Sem A G Engels, Amy Goodale, Jasper van der Lugt, Tanaz Abid, Li Wang, Kevin N Zhou, Jayne Vogelzang, Keith L Ligon, Timothy N Phoenix, Jennifer A Roth, David E Root, Norbert Hubner, Todd R Golub, Pratiti Bandopadhayay, Sebastiaan van Heesch, John R Prensner
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...
December 29, 2023: Molecular Cell