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Oncogenic translation directs spliceosome dynamics revealing an integral role for SF3A3 in breast cancer
- Source :
- Molecular Cell, 81(7):j.molcel.2021.01.034, 1453-1468. CELL PRESS
- Publication Year :
- 2021
-
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.
- Subjects :
- Adult
translation control
cancer stem cells
Spliceosome
Carcinogenesis
Mice, Nude
Breast Neoplasms
SF3A3
MYC
DRP1
Biology
medicine.disease_cause
Malignant transformation
Proto-Oncogene Proteins c-myc
Mice
03 medical and health sciences
alternative splicing
0302 clinical medicine
Cancer stem cell
eIF3D
medicine
Animals
Humans
Molecular Biology
Aged
030304 developmental biology
Aged, 80 and over
0303 health sciences
Alternative splicing
RNA
Translation (biology)
Cell Biology
Middle Aged
mitochondrial dynamics
Cell biology
Protein Biosynthesis
RNA splicing
Neoplastic Stem Cells
Spliceosomes
triple-negative breast cancer
Female
cancer plasticity
RNA Splicing Factors
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 10972765
- Database :
- OpenAIRE
- Journal :
- Molecular Cell, 81(7):j.molcel.2021.01.034, 1453-1468. CELL PRESS
- Accession number :
- edsair.doi.dedup.....9df2847fe43c27cd85566e4b0e55bf3a