title: Intracellular and extracellular microRNA: An update on localization and biological role.
abstract: MicroRNA (miRNA) is a class of small non-coding RNAs which mediate post-transcriptional gene silencing (PTGS) by sequence-specific inhibition of target mRNAs translation and/or lowering their half-lives in the cytoplasm. Together with their binding partners, Argonaute (AGO) proteins, miRNAs form cores of RNA-induced silencing complexes (RISC). Despite a substantial progress in understanding RISC structure, until recently little was known about its localization in the cell. This review is aimed to provide an overview of the emerging picture of miRNA and RISC localization and function both in the intracellular space and outside of the cell. In contrast to the common assumption that PTGS occurs in the cytoplasm, it was found to operate mainly on the membranes of the endoplasmic reticulum (ER). Besides ER membranes miRNAs were found in all main cellular compartments including nucleus, nucleolus and mitochondria where they regulate various processes including transcription, translation, alternative splicing and DNA repair. Moreover, a certain pool of miRNAs may not be associated with RISC and carry completely different functions. Finally, the discovery of cell-free miRNAs in all biological fluids suggests that miRNAs might also act as signaling molecules outside the cell, and may be utilized as biomarkers for a variety of diseases. In this review we discuss miRNA secretion mechanisms and possible pathways of cell-cell communication via miRNA-containing exosomes in vivo.
authors.affiliation: Hertsen Moscow Oncology Research Institute, Branch of the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, 125284, Moscow, Russian Federation; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russian Federation. Electronic address: j-makarova@yandex.ru.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Makarova
authors.affiliation: Hertsen Moscow Oncology Research Institute, Branch of the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, 125284, Moscow, Russian Federation.
authors.forename: Maxim U
authors.initials: MU
authors.lastname: Shkurnikov
authors.affiliation: Department of Anatomy and Experimental Morphology, University Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistr. 52, Hamburg D-20246, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wicklein
authors.affiliation: Department of Anatomy and Experimental Morphology, University Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistr. 52, Hamburg D-20246, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Lange
authors.affiliation: SRC Bioclinicum, Ugreshskaya str 2/85, 115088 Moscow, Russian Federation; Moscow State University of Mechanical Engineering, Bolshaya Semenovskaya str 38, 107023 Moscow, Russian Federation.
authors.forename: Timur R
authors.initials: TR
authors.lastname: Samatov
authors.affiliation: Molecular Epidemiology Group, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Turchinovich
authors.affiliation: Hertsen Moscow Oncology Research Institute, Branch of the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, 125284, Moscow, Russian Federation. Electronic address: tonevitsky@mail.ru.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Tonevitsky
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics* / Q000378:metabolism; D002450:Cell Communication; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D014176:Protein Biosynthesis; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D060565:Argonaute Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D034743:RNA-Induced Silencing Complex
keywords: Cancer; Circulating microRNA; Exosomes; Post-transcriptional gene silencing; microRNA biomarkers; microRNA function