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Cell Rep. 2016 Oct 11;17(3):799-808. doi: 10.1016/j.celrep.2016.09.031.

The RNA-Binding Protein SYNCRIP Is a Component of the Hepatocyte Exosomal Machinery Controlling MicroRNA Sorting.

Author information

1
Department of Cellular Biotechnologies and Haematology, Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy; National Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense 292, 00149 Rome, Italy.
2
Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry, Schola Medica Salernitana, University of Salerno, Via Salvador Allende 1, 84081 Baronissi, Italy.
3
Department of Cellular Biotechnologies and Haematology, Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
4
National Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense 292, 00149 Rome, Italy.
5
Department of Cellular Biotechnologies and Haematology, Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy; National Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense 292, 00149 Rome, Italy. Electronic address: tripodi@bce.uniroma1.it.

Abstract

Despite clear evidence that exosomal microRNAs (miRNAs) are able to modulate the cellular microenvironment and that exosomal RNA cargo selection is deregulated in pathological conditions, the mechanisms controlling specific RNA sorting into extracellular vesicles are still poorly understood. Here, we identified the RNA binding protein SYNCRIP (synaptotagmin-binding cytoplasmic RNA-interacting protein; also known as hnRNP-Q or NSAP1) as a component of the hepatocyte exosomal miRNA sorting machinery. SYNCRIP knockdown impairs sorting of miRNAs in exosomes. Furthermore, SYNCRIP directly binds to specific miRNAs enriched in exosomes sharing a common extra-seed sequence (hEXO motif). The hEXO motif has a role in the regulation of miRNA localization, since embedment of this motif into a poorly exported miRNA enhances its loading into exosomes. This evidence provides insights into the mechanisms of miRNA exosomal sorting process. Moreover, these findings open the way for the possible selective modification of the miRNAs exosomal cargo.

KEYWORDS:

NSAP1; exosomes; hnRNPA2B1; hnRNPQ; microRNA

PMID:
27732855
DOI:
10.1016/j.celrep.2016.09.031
[Indexed for MEDLINE]
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