6ES4

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

Summary for 6ES4

• Entry DOI: 10.2210/pdb6es4/pdb
• Descriptor: Syncrip, isoform K, SULFATE ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: mirna, exosome, syncrip, rna-binding, rna
• Biological source: Drosophila melanogaster (Fruit fly)
• Total number of polymer chains: 2
• Total formula weight: 50675.56

Authors

Hobor, F.,Dallmann, A.,Ball, N.J.,Cicchini, C.,Battistelli, C.,Ogrodowicz, R.W.,Christodoulou, E.,Martin, S.R.,Castello, A.,Tripodi, M.,Taylor, I.A.,Ramos, A. (deposition date: 2017-10-19, release date: 2018-03-07, Last modification date: 2024-10-23)

Primary citation

Hobor, F.,Dallmann, A.,Ball, N.J.,Cicchini, C.,Battistelli, C.,Ogrodowicz, R.W.,Christodoulou, E.,Martin, S.R.,Castello, A.,Tripodi, M.,Taylor, I.A.,Ramos, A.
A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets.
Nat Commun, 9:831-831, 2018

PubMed 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.

PubMed: 29483512
DOI: 10.1038/s41467-018-03182-3

Experimental method

X-RAY DIFFRACTION (2.2 Å)