A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets.

Autor: Hobor F; Research Department of Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London, WC1E 6XA, UK.; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK., Dallmann A; Research Department of Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London, WC1E 6XA, UK.; Department of Chemistry, Humboldt Universität zu Berlin, Brook-Taylor-Street 2, 12489, Berlin, Germany., Ball NJ; Macromolecular Structure Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Cicchini C; Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy., Battistelli C; Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy., Ogrodowicz RW; Structural Biology Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Christodoulou E; Structural Biology Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Martin SR; Structural Biology Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Castello A; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Tripodi M; Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy., Taylor IA; Macromolecular Structure Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK. Ian.Taylor@crick.ac.uk., Ramos A; Research Department of Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London, WC1E 6XA, UK. a.ramos@ucl.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2018 Feb 26; Vol. 9 (1), pp. 831. Date of Electronic Publication: 2018 Feb 26.
DOI: 10.1038/s41467-018-03182-3
Abstrakt: Exosomal miRNA transfer is a mechanism for cell-cell communication that is important in the immune response, in the functioning of the nervous system and in cancer. Syncrip/hnRNPQ is a highly conserved RNA-binding protein that mediates the exosomal partition of a set of miRNAs. Here, we report that Syncrip's amino-terminal domain, which was previously thought to mediate protein-protein interactions, is a cryptic, conserved and sequence-specific RNA-binding domain, designated NURR (N-terminal unit for RNA recognition). The NURR domain mediates the specific recognition of a short hEXO sequence defining Syncrip exosomal miRNA targets, and is coupled by a non-canonical structural element to Syncrip's RRM domains to achieve high-affinity miRNA binding. As a consequence, Syncrip-mediated selection of the target miRNAs implies both recognition of the hEXO sequence by the NURR domain and binding of the RRM domains 5' to this sequence. This structural arrangement enables Syncrip-mediated selection of miRNAs with different seed sequences.
Databáze: MEDLINE