RNA binding protein CUGBP2/ETR-3 regulates STAT3 alternative splicing.

Autor: Kise M; Laboratory of Molecular Medicinal Science, Department of Pharmaceutical Sciences, Ritsumeikan University, Shiga, Japan; Graduate School of Pharmacy, Ritsumeikan University, Shiga, Japan., Masaki S; Laboratory of Molecular Medicinal Science, Department of Pharmaceutical Sciences, Ritsumeikan University, Shiga, Japan; Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan. Electronic address: smasaki@g.ecc.u-tokyo.ac.jp., Kataoka N; Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan., Suzuki K; Laboratory of Molecular Medicinal Science, Department of Pharmaceutical Sciences, Ritsumeikan University, Shiga, Japan. Electronic address: kenjiszk@ph.ritsumei.ac.jp.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Dec 20; Vol. 739, pp. 151000. Date of Electronic Publication: 2024 Nov 14.
DOI: 10.1016/j.bbrc.2024.151000
Abstrakt: Signal transducer and activator of transcription 3 (STAT3) is a multifactorial regulator involved in many biological responses. Alternative splicing of STAT3 pre-mRNA leads to an internal 50-nucleotide deletion of exon 23 selecting an alternative 3' acceptor site, resulting in the generation of two splicing isoforms, STAT3α and STAT3β. STAT3β lacks 55 amino acid-residue transactivation domain at the C-terminal of STAT3α replacing seven unique amino acids. Although STAT3β was originally thought to be a dominant negative isoform of STAT3α, accumulating evidence have shown that STAT3β possesses both its unique functions and those that overlap with STAT3α in fundamental cellular processes. However, much remains unknown about STAT3 pre-mRNA alternative splicing in determining the balance between STAT3 isoforms. In this study, we identified cis-regulatory elements and CUGBP2/ETR-3 as a novel trans-acting factor that regulates STAT3 alternative splicing. Our findings demonstrate that STAT3 splicing can be modulated by CUGBP2 via association with UG-rich elements of intron 22, providing a novel insight into the mechanism of STAT3 alternative splicing. CUGBP2 would be a crucial molecule regulating the balance of STAT3 isoform expression, thus targeting CUGBP2 and its recognition sequences in intron 22 of STAT3 might impact on various biological processes regulated by STAT3 signaling pathway.
Competing Interests: Declaration of competing interest All authors of this manuscript have no conflicts of interest to declare.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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