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

Hobor, F., Dallmann, A., Ball, N. J., Cicchini, C., Battistelli, C., Ogrodowicz, R. W., Christodoulou, E., Martin, S. R. and Castello, A. (2018) A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets. Nature Communications, 9, 831. (doi: 10.1038/s41467-018-03182-3) (PMID:29483512) (PMCID:PMC5827114)

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Abstract

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.

Item Type:Articles
Additional Information:This work was funded by the UK Medical Research Council grant MC_PC_13051. It was also supported by University College London and by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001178) the UK Medical Research Council (FC001178) and the Wellcome trust (FC001178). It was also funded by the Associazione Italiana per la Ricerca sul Cancro (AIRC; grant 18843), Pasteur Institute-Cenci Bolognetti Foundation and Sapienza University of Rome (RG11715C34754712).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Castello, Professor Alfredo
Authors: Hobor, F., Dallmann, A., Ball, N. J., Cicchini, C., Battistelli, C., Ogrodowicz, R. W., Christodoulou, E., Martin, S. R., and Castello, A.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Nature Communications
Publisher:Nature Research
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © The Author(s) 2018
First Published:First published in Nature Communications 9:831
Publisher Policy:Reproduced under a Creative Commons license

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