Circulating miRNAs: cell-cell communication function?

A Turchinovich, T R Samatov, A G Tonevitsky, B Burwinkel, A Turchinovich, T R Samatov, A G Tonevitsky, B Burwinkel

Abstract

Nuclease resistant extracellular miRNAs have been found in all known biological fluids. The biological function of extracellular miRNAs remains questionable; however, strong evidence suggests that these miRNAs can be more than just byproducts of cellular activity. Some extracellular miRNA species might carry cell-cell signaling function during various physiological and pathological processes. In this review, we discuss the state-of-the-art in the field of intercellular miRNA transport and highlight current theories regarding the origin and the biological function of extracellular miRNAs.

Keywords: HDL; argonaute proteins; biofluids; biomarkers; cell communication; exosomes; miRNA; microvesicles.

Figures

Figure 1
Figure 1
The biogenesis of miRNAs starts in the cell nucleus with generation of primary miRNAs (pri-miRNAs) transcripts. Pri-miRNAs are cleaved by the microprocessor complex Drosha/DGCR8 into shorter miRNA precursors (pre-miRNA). The later are transported to the cytoplasm and further cut by the endonuclease Dicer into ~22 nt miRNA/miRNA* duplexes. Finally, one of the miRNA/miRNA* strands is incorporated into a protein of the Argonaute family (AGO1, AGO2, AGO3, or AGO4). The mature miRNA strand eventually serves as the guide for RISC-mediated mRNA targeting resulting in either mRNA cleavage or translational interference. Extracellular miRNA can be either solely AGO protein-associated or additionally encapsulated into apoptotic bodies, microvesicles, and HDL particles.

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