期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 78, 期 4, 页码 1745-1763出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-020-03610-y
关键词
RNA-binding protein; Nuclear body; Intersectin; SAM68; SH3 domain; RNA; Proline-Rich Motif; Membraneless compartments
资金
- Genopole Evry
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Eiffel Excellence Scholarship Program
- French embassy in Ukraine
- FRR programs from the UEVE
SAM68 is an mRNA-binding protein involved in mRNA processing in the nucleus, and its interaction with ITSN1 can enhance its solubility, regulating the processing of a fraction of nuclear mRNAs. ITSN1 and mRNA may act together to promote SAM68 solubilization, which is important for SAM68-controlled splicing events related to higher neuronal functions or cancer progression.
SAM68 is an mRNA-binding protein involved in mRNA processing in the nucleus that forms membraneless compartments called SAM68 Nuclear Bodies (SNBs). We found that intersectin 1 (ITSN1), a multidomain scaffold protein harboring five soluble SH3 domains, interacts with SAM68 proline-rich motifs (PRMs) surrounded by self-adhesive low complexity domains. While SAM68 is poorly soluble in vitro, the interaction of ITSN1 SH3 domains and mRNA with SAM68 enhances its solubility. In HeLa cells, the interaction between the first ITSN1 SH3 domain (SH3A) and P0, the N-terminal PRM of SAM68, induces the dissociation of SNBs. In addition, we reveal the ability of another SH3 domain (SH3D) of ITSN1 to bind to mRNAs. ITSN1 and mRNA may thus act in concert to promote SAM68 solubilization, consistent with the absence of mRNA in SNBs in cells. Together, these results support the notion of a specific chaperoning of PRM-rich SAM68 within nuclear ribonucleoprotein complexes by ITSN1 that may regulate the processing of a fraction of nuclear mRNAs, notably SAM68-controlled splicing events related to higher neuronal functions or cancer progression. This observation may also serve as a putative model of the interaction between other PRM-rich RBPs and signaling proteins harboring SH3 domains.
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