Stress-induced lncRNA LASTR fosters cancer cell fitness by regulating the activity of the U4/U6 recycling factor SART3.
Animals
Antigens, Neoplasm
/ metabolism
Cell Hypoxia
Cell Line, Tumor
Epithelial Cells
/ metabolism
Gene Expression Regulation, Neoplastic
Genes, Essential
Humans
Introns
/ genetics
MAP Kinase Signaling System
Mice, Nude
Neoplasms
/ genetics
RNA Splicing
/ genetics
RNA, Long Noncoding
/ genetics
RNA-Binding Proteins
/ metabolism
Ribonucleoprotein, U4-U6 Small Nuclear
/ metabolism
Stress, Physiological
Up-Regulation
/ genetics
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
18 03 2020
18 03 2020
Historique:
accepted:
15
01
2020
revised:
24
11
2019
received:
26
04
2019
pubmed:
21
1
2020
medline:
19
5
2020
entrez:
21
1
2020
Statut:
ppublish
Résumé
Dysregulated splicing is a common event in cancer even in the absence of mutations in the core splicing machinery. The aberrant long non-coding transcriptome constitutes an uncharacterized level of regulation of post-transcriptional events in cancer. Here, we found that the stress-induced long non-coding RNA (lncRNA), LINC02657 or LASTR (lncRNA associated with SART3 regulation of splicing), is upregulated in hypoxic breast cancer and is essential for the growth of LASTR-positive triple-negative breast tumors. LASTR is upregulated in several types of epithelial cancers due to the activation of the stress-induced JNK/c-JUN pathway. Using a mass-spectrometry based approach, we identified the RNA-splicing factor SART3 as a LASTR-interacting partner. We found that LASTR promotes splicing efficiency by controlling SART3 association with the U4 and U6 small nuclear ribonucleoproteins (snRNP) during spliceosome recycling. Intron retention induced by LASTR depletion downregulates expression of essential genes, ultimately decreasing the fitness of cancer cells.
Identifiants
pubmed: 31956895
pii: 5709714
doi: 10.1093/nar/gkz1237
pmc: PMC7049684
doi:
Substances chimiques
Antigens, Neoplasm
0
RNA, Long Noncoding
0
RNA-Binding Proteins
0
Ribonucleoprotein, U4-U6 Small Nuclear
0
SART3 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2502-2517Commentaires et corrections
Type : ErratumIn
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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