The RNA-Binding Protein SYNCRIP Is a Component of the Hepatocyte Exosomal Machinery Controlling MicroRNA Sorting
Laura Santangelo,
Giorgio Giurato,
Carla Cicchini,
Claudia Montaldo,
Carmine Mancone,
Roberta Tarallo,
Cecilia Battistelli,
Tonino Alonzi,
Alessandro Weisz,
Marco Tripodi
Affiliations
Laura Santangelo
Department of Cellular Biotechnologies and Haematology, Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
Giorgio Giurato
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
Carla Cicchini
Department of Cellular Biotechnologies and Haematology, Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
Claudia Montaldo
National Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense 292, 00149 Rome, Italy
Carmine Mancone
Department of Cellular Biotechnologies and Haematology, Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
Roberta Tarallo
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
Cecilia Battistelli
Department of Cellular Biotechnologies and Haematology, Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
Tonino Alonzi
National Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense 292, 00149 Rome, Italy
Alessandro Weisz
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
Marco Tripodi
Department of Cellular Biotechnologies and Haematology, Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
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.
