ITSN1 regulates SAM68 solubility through SH3 domain interactions with SAM68 proline-rich motifs
| Autor: | Pankivskyi, S., Pastré, D., Steiner, E., Joshi, V., Rynditch, A., Hamon, L. |
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| Přispěvatelé: | Structure et activité des biomolécules normales et pathologiques (SABNP), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institute of Molecular Biology and Genetics of NAS of Ukraine, National Academy of Sciences of Ukraine (NASU), Maciejak, Olek |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Proline
RNA Splicing RNA-binding protein Amino Acid Motifs SAM68 SH3 domain Nuclear body src Homology Domains Proline-Rich Motif [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Amino Acid Sequence Adaptor Proteins Signal Transducing Cell Nucleus RNA-Binding Proteins Intersectin Endocytosis DNA-Binding Proteins Adaptor Proteins Vesicular Transport Solubility Membraneless compartments RNA Original Article Carrier Proteins HeLa Cells Protein Binding |
| Zdroj: | Cellular and Molecular Life Sciences Cellular and Molecular Life Sciences, 2021, 78, pp.1745-1763. ⟨10.1007/s00018-020-03610-y⟩ Cellular and Molecular Life Sciences, Springer Verlag, 2021, 78 (1745-1763), ⟨10.1007/s00018-020-03610-y⟩ |
| ISSN: | 1420-682X 1420-9071 |
| Popis: | 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. Electronic supplementary material The online version of this article (10.1007/s00018-020-03610-y) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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