Oncogenic translation directs spliceosome dynamics revealing an integral role for SF3A3 in breast cancer
(2021) In Molecular Cell 81(7).- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/978ceb5e-9e86-447a-859b-4cc95e7c7425
- author
- Ciesla, Maciej
LU
; Cao Thi Ngoc, Phuong
LU
; Cordero Concha, Maria Eugenia
LU
; Sejas Martínez, Álvaro
LU
; Morsing, Mikkel
LU
; Muthukumar, Sowndarya
LU
; Beneventi, Giulia
LU
; Madej, Magdalena
LU
; Munita, Roberto
LU
; Jönsson, Terese
LU
; Lövgren, Kristina
LU
; Ebbesson, Anna
LU
; Nodin, Björn
LU
; Hedenfalk, Ingrid
LU
; Jirström, Karin
LU
; Vallon-Christersson, Johan
LU
; Honeth, Gabriella
LU
; Staaf, Johan
LU
; Incarnato, Danny
; Pietras, Kristian
LU
; Bosch Campos, Ana
LU
and Bellodi, Cristian
LU
(Less) - organization
- publishing date
- 2021-04-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- DRP1, MYC, SF3A3, alternative splicing, cancer plasticity, cancer stem cells, eIF3D, mitochondrial dynamics, translation control, triple-negative breast cancer
- in
- Molecular Cell
- volume
- 81
- issue
- 7
- pages
- 28 pages
- publisher
- Cell Press
- external identifiers
-
- scopus:85103309675
- pmid:33662273
- ISSN
- 1097-2765
- DOI
- 10.1016/j.molcel.2021.01.034
- language
- English
- LU publication?
- yes
- id
- 978ceb5e-9e86-447a-859b-4cc95e7c7425
- date added to LUP
- 2021-10-10 15:41:28
- date last changed
- 2024-01-29 02:55:52
@article{978ceb5e-9e86-447a-859b-4cc95e7c7425,
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.}},
author = {{Ciesla, Maciej and Cao Thi Ngoc, Phuong and Cordero Concha, Maria Eugenia and Sejas Martínez, Álvaro and Morsing, Mikkel and Muthukumar, Sowndarya and Beneventi, Giulia and Madej, Magdalena and Munita, Roberto and Jönsson, Terese and Lövgren, Kristina and Ebbesson, Anna and Nodin, Björn and Hedenfalk, Ingrid and Jirström, Karin and Vallon-Christersson, Johan and Honeth, Gabriella and Staaf, Johan and Incarnato, Danny and Pietras, Kristian and Bosch Campos, Ana and Bellodi, Cristian}},
issn = {{1097-2765}},
keywords = {{DRP1; MYC; SF3A3; alternative splicing; cancer plasticity; cancer stem cells; eIF3D; mitochondrial dynamics; translation control; triple-negative breast cancer}},
language = {{eng}},
month = {{04}},
number = {{7}},
publisher = {{Cell Press}},
series = {{Molecular Cell}},
title = {{Oncogenic translation directs spliceosome dynamics revealing an integral role for SF3A3 in breast cancer}},
url = {{http://dx.doi.org/10.1016/j.molcel.2021.01.034}},
doi = {{10.1016/j.molcel.2021.01.034}},
volume = {{81}},
year = {{2021}},
}