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SHR Neuro Cancer Cardio Lipid Metab Microb

Klec, C; Knutsen, E; Schwarzenbacher, D; Jonas, K; Pasculli, B; Heitzer, E; Rinner, B; Krajina, K; Prinz, F; Gottschalk, B; Ulz, P; Deutsch, A; Prokesch, A; Jahn, SW; Lellahi, SM; Perander, M; Barbano, R; Graier, WF; Parrella, P; Calin, GA; Pichler, M.
ALYREF, a novel factor involved in breast carcinogenesis, acts through transcriptional and post-transcriptional mechanisms selectively regulating the short NEAT1 isoform.
Cell Mol Life Sci. 2022; 79(7): 391 Doi: 10.1007/s00018-022-04402-2 [OPEN ACCESS]
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Leading authors Med Uni Graz
Klec Christiane
Pichler Martin
Co-authors Med Uni Graz
Deutsch Alexander
Gottschalk Benjamin
Graier Wolfgang
Heitzer Ellen
Jahn Stephan
Jonas Katharina
Krajina Katarina
Ninaus Daniela
Prinz Felix
Prokesch Andreas
Rinner Beate

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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.

Find related publications in this database (Keywords)
Breast cancer
Transcriptional regulation
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