ALYREF, a novel factor involved in breast carcinogenesis, acts through transcriptional and post-transcriptional mechanisms selectively regulating the short NEAT1 isoform.
ALYREF
Breast cancer
NEAT1
Transcriptional regulation
lncRNA
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
01 Jul 2022
01 Jul 2022
Historique:
received:
01
12
2021
accepted:
25
05
2022
revised:
15
05
2022
entrez:
1
7
2022
pubmed:
2
7
2022
medline:
7
7
2022
Statut:
epublish
Résumé
The RNA-binding protein ALYREF (THOC4) is involved in transcriptional regulation and nuclear mRNA export, though its role and molecular mode of action in breast carcinogenesis are completely unknown. Here, we identified high ALYREF expression as a factor for poor survival in breast cancer patients. ALYREF significantly influenced cellular growth, apoptosis and mitochondrial energy metabolism in breast cancer cells as well as breast tumorigenesis in orthotopic mouse models. Transcriptional profiling, phenocopy and rescue experiments identified the short isoform of the lncRNA NEAT1 as a molecular trigger for ALYREF effects in breast cancer. Mechanistically, we found that ALYREF binds to the NEAT1 promoter region to enhance the global NEAT1 transcriptional activity. Importantly, by stabilizing CPSF6, a protein that selectively activates the post-transcriptional generation of the short isoform of NEAT1, as well as by direct binding and stabilization of the short isoform of NEAT1, ALYREF selectively fine-tunes the expression of the short NEAT1 isoform. Overall, our study describes ALYREF as a novel factor contributing to breast carcinogenesis and identifies novel molecular mechanisms of regulation the two isoforms of NEAT1.
Identifiants
pubmed: 35776213
doi: 10.1007/s00018-022-04402-2
pii: 10.1007/s00018-022-04402-2
pmc: PMC9249705
doi:
Substances chimiques
ALYREF protein, human
0
NEAT1 long non-coding RNA, human
0
Nuclear Proteins
0
Protein Isoforms
0
RNA, Long Noncoding
0
RNA-Binding Proteins
0
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
391Subventions
Organisme : Austrian Science Fund FWF
ID : W 1226
Pays : Austria
Informations de copyright
© 2022. The Author(s).
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