Santangelo Laura, Giurato Giorgio, Cicchini Carla, Montaldo Claudia, Mancone Carmine, Tarallo Roberta, Battistelli Cecilia, Alonzi Tonino, Weisz Alessandro, Tripodi Marco
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.
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.
Cell Rep. 2016 Oct 11;17(3):799-808. doi: 10.1016/j.celrep.2016.09.031.
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.
尽管有明确证据表明外泌体微小RNA（miRNA）能够调节细胞微环境，且在病理条件下外泌体RNA货物选择失调，但控制特定RNA分选到细胞外囊泡中的机制仍知之甚少。在此，我们鉴定出RNA结合蛋白SYNCRIP（突触结合蛋白结合细胞质RNA相互作用蛋白；也称为hnRNP-Q或NSAP1）是肝细胞外泌体miRNA分选机制的一个组成部分。SYNCRIP敲低会损害外泌体中miRNA的分选。此外，SYNCRIP直接结合富含共同额外种子序列（hEXO基序）的外泌体中特异性miRNA。hEXO基序在miRNA定位调节中起作用，因为将该基序嵌入难以输出的miRNA中会增强其装载到外泌体中的能力。这一证据为miRNA外泌体分选过程的机制提供了见解。此外，这些发现为可能对外泌体miRNA货物进行选择性修饰开辟了道路。
