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

Fruzsina Hobor, Andre Dallmann, Neil J. Ball, Carla Cicchini, Cecilia Battistelli, Roksana W. Ogrodowicz, Evangelos Christodoulou, Stephen R. Martin, Alfredo Castello, Marco Tripodi, Ian A. Taylor () and Andres Ramos ()
Additional contact information
Fruzsina Hobor: University College London, Darwin Building
Andre Dallmann: University College London, Darwin Building
Neil J. Ball: The Francis Crick Institute
Carla Cicchini: Sapienza University of Rome
Cecilia Battistelli: 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: Sapienza University of Rome
Ian A. Taylor: The Francis Crick Institute
Andres Ramos: University College London, Darwin Building

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03182-3

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