
Kristian Pietras
Research team manager

Oncogenic translation directs spliceosome dynamics revealing an integral role for SF3A3 in breast cancer
Author
Summary, in English
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.
Department/s
- Division of Molecular Hematology (DMH)
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- LUCC: Lund University Cancer Centre
- Division of Translational Cancer Research
Publishing year
2021-04-01
Language
English
Publication/Series
Molecular Cell
Volume
81
Issue
7
Document type
Journal article
Publisher
Cell Press
Topic
- Cell and Molecular Biology
- Biochemistry and Molecular Biology
- Cancer and Oncology
Keywords
- DRP1
- MYC
- SF3A3
- alternative splicing
- cancer plasticity
- cancer stem cells
- eIF3D
- mitochondrial dynamics
- translation control
- triple-negative breast cancer
Status
Published
ISBN/ISSN/Other
- ISSN: 1097-2765