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

DOI: 10.1038/s41467-018-03182-3 DOI Help

Authors: Fruzsina Hobor (University College London) , Andre Dallmann (University College London) , Neil J. Ball (The Francis Crick Institute) , Carla Cicchini (Instituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome) , Cecilia Battistelli (Instituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome) , Roksana W. Ogrodowicz (The Francis Crick Institute) , Evangelos Christodoulou (The Francis Crick Institute) , Stephen R. Martin (The Francis Crick Institute) , Alfredo Castello (University of Oxford) , Marco Tripodi (Instituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome) , Ian A. Taylor (The Francis Crick Institute) , Andres Ramos (University College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 9

State: Published (Approved)
Published: February 2018
Diamond Proposal Number(s): 13775

Open Access Open Access

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.

Journal Keywords: Extracellular signalling molecules; miRNAs; Solution-state NMR; X-ray crystallography

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography

Added On: 01/03/2018 08:18


Discipline Tags:

Life Sciences & Biotech Structural biology

Technical Tags:

Diffraction Macromolecular Crystallography (MX)