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

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...

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Main Authors: Hobor, F, Dallmann, A, Ball, NJ, Cicchini, C, Battistelli, C, Ogrodowicz, RW, Christodoulou, E, Martin, SR, Castello, A, Tripodi, M, Taylor, IA, Ramos, A
Format: Journal article
Published: Nature Publishing Group 2018
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author Hobor, F
Dallmann, A
Ball, NJ
Cicchini, C
Battistelli, C
Ogrodowicz, RW
Christodoulou, E
Martin, SR
Castello, A
Tripodi, M
Taylor, IA
Ramos, A
author_facet Hobor, F
Dallmann, A
Ball, NJ
Cicchini, C
Battistelli, C
Ogrodowicz, RW
Christodoulou, E
Martin, SR
Castello, A
Tripodi, M
Taylor, IA
Ramos, A
author_sort Hobor, F
collection OXFORD
description 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.
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spelling oxford-uuid:8868b05f-8a23-472a-a949-7007352951692022-03-26T22:17:08ZA cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targetsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8868b05f-8a23-472a-a949-700735295169Symplectic Elements at OxfordNature Publishing Group2018Hobor, FDallmann, ABall, NJCicchini, CBattistelli, COgrodowicz, RWChristodoulou, EMartin, SRCastello, ATripodi, MTaylor, IARamos, AExosomal 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.
spellingShingle Hobor, F
Dallmann, A
Ball, NJ
Cicchini, C
Battistelli, C
Ogrodowicz, RW
Christodoulou, E
Martin, SR
Castello, A
Tripodi, M
Taylor, IA
Ramos, A
A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets
title A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets
title_full A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets
title_fullStr A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets
title_full_unstemmed A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets
title_short A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets
title_sort cryptic rna binding domain mediates syncrip recognition and exosomal partitioning of mirna targets
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