title: The RNA-Binding Protein SYNCRIP Is a Component of the Hepatocyte Exosomal Machinery Controlling MicroRNA Sorting.
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.
authors.affiliation: 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.
authors.forename: Laura
authors.initials: L
authors.lastname: Santangelo
authors.affiliation: 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.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giurato
authors.affiliation: Department of Cellular Biotechnologies and Haematology, Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Cicchini
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense 292, 00149 Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Montaldo
authors.affiliation: 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.
authors.forename: Carmine
authors.initials: C
authors.lastname: Mancone
authors.affiliation: 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.
authors.forename: Roberta
authors.initials: R
authors.lastname: Tarallo
authors.affiliation: Department of Cellular Biotechnologies and Haematology, Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Battistelli
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense 292, 00149 Rome, Italy.
authors.forename: Tonino
authors.initials: T
authors.lastname: Alonzi
authors.affiliation: 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.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Weisz
authors.affiliation: 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.
authors.forename: Marco
authors.initials: M
authors.lastname: Tripodi
mesh_terms: D000818:Animals; D001483:Base Sequence; D055354:Exosomes / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000378:metabolism*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D059372:Nucleotide Motifs / Q000235:genetics; D034443:RNA Transport / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C486049:Syncrip protein, mouse; C439768:hnRNP A2
keywords: NSAP1; exosomes; hnRNPA2B1; hnRNPQ; microRNA