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The origin, function, and diagnostic potential of extracellular microRNAs in human body fluids

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Recently, numerous studies have documented the importance of microRNAs (miRNAs) as an essential cornerstone of the genetic system. Although RNA is usually considered an unstable molecule because of the ubiquitous ribonuclease, miRNAs are now known to circulate in the bloodstream and other body fluids in a stable, cell‐free form. Importantly, extracellular miRNAs are aberrantly present in plasma, serum, and other body fluids during the pathogenesis of many diseases and, thus, are promising noninvasive or minimally invasive biomarkers to assess the pathological status of the body. However, the origin and biological function of extracellular miRNAs remains incompletely understood. In this review, we summarize the recent literature on the biogenesis and working models of extracellular miRNAs, and we highlight the impact of extending these ongoing extracellular miRNA studies to clinical applications. WIREs RNA 2014, 5:285–300. doi: 10.1002/wrna.1208 This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs

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The modes of extracellular microRNA (miRNA) packaging. After being processed into the mature form, some miRNAs can bind to complementary sequences on target messenger RNAs (mRNAs) to repress translation or trigger mRNA cleavage. Other miRNAs are packaged and transported to the extracellular environment via three different pathways: (1) enclosure within membranous vesicles, including exosomes and shedding vesicles; (2) association with lipoproteins, such as high‐density lipoprotein (HDL); or (3) association with RNA‐binding proteins, such as Argonaute2 (AGO2) and nucleophosmin 1 (NPM1).
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RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs

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