@article{978ceb5e9e86447a859b4cc95e7c7425,
title = "Oncogenic translation directs spliceosome dynamics revealing an integral role for SF3A3 in breast cancer",
abstract = "Splicing is a central RNA-based process commonly altered in human cancers; however, how spliceosomal components are co-opted during tumorigenesis remains poorly defined. Here we unravel the core splice factor SF3A3 at the nexus of a translation-based program that rewires splicing during malignant transformation. Upon MYC hyperactivation, SF3A3 levels are modulated translationally through an RNA stem-loop in an eIF3D-dependent manner. This ensures accurate splicing of mRNAs enriched for mitochondrial regulators. Altered SF3A3 translation leads to metabolic reprogramming and stem-like properties that fuel MYC tumorigenic potential in vivo. Our analysis reveals that SF3A3 protein levels predict molecular and phenotypic features of aggressive human breast cancers. These findings unveil a post-transcriptional interplay between splicing and translation that governs critical facets of MYC-driven oncogenesis.",
keywords = "DRP1, MYC, SF3A3, alternative splicing, cancer plasticity, cancer stem cells, eIF3D, mitochondrial dynamics, translation control, triple-negative breast cancer",
author = "Maciej Ciesla and {Cao Thi Ngoc}, Phuong and {Cordero Concha}, {Maria Eugenia} and {Sejas Mart{\'i}nez}, {\'A}lvaro and Mikkel Morsing and Sowndarya Muthukumar and Giulia Beneventi and Magdalena Madej and Roberto Munita and Terese J{\"o}nsson and Kristina L{\"o}vgren and Anna Ebbesson and Bj{\"o}rn Nodin and Ingrid Hedenfalk and Karin Jirstr{\"o}m and Johan Vallon-Christersson and Gabriella Honeth and Johan Staaf and Danny Incarnato and Kristian Pietras and {Bosch Campos}, Ana and Cristian Bellodi",
year = "2021",
month = apr,
day = "1",
doi = "10.1016/j.molcel.2021.01.034",
language = "English",
volume = "81",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "7",
}