Format

Send to

Choose Destination
Prog Histochem Cytochem. 2016 Nov;51(3-4):33-49. doi: 10.1016/j.proghi.2016.06.001. Epub 2016 Jun 25.

Intracellular and extracellular microRNA: An update on localization and biological role.

Author information

1
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.
2
Hertsen Moscow Oncology Research Institute, Branch of the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, 125284, Moscow, Russian Federation.
3
Department of Anatomy and Experimental Morphology, University Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistr. 52, Hamburg D-20246, Germany.
4
SRC Bioclinicum, Ugreshskaya str 2/85, 115088 Moscow, Russian Federation; Moscow State University of Mechanical Engineering, Bolshaya Semenovskaya str 38, 107023 Moscow, Russian Federation.
5
Molecular Epidemiology Group, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
6
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.

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.

KEYWORDS:

Cancer; Circulating microRNA; Exosomes; Post-transcriptional gene silencing; microRNA biomarkers; microRNA function

PMID:
27396686
DOI:
10.1016/j.proghi.2016.06.001
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center