Sources and Functions of Extracellular Small RNAs in Human Circulation.

Sources and Functions of Extracellular Small RNAs in Human Circulation.
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DOI:
10.1146/annurev-nutr-071715-050711
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发表时间:
2016-07-17
影响因子:
8.9
通讯作者:
Wilmes P
Wilmes P
中科院分区:
医学2区
文献类型:
--
作者:
Fritz JV;Heintz-Buschart A;Ghosal A;Wampach L;Etheridge A;Galas D;Wilmes P

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在人体循环中已检测到各种生物型的内源小RNA (sRNA),包括microRNA、tRNA、rRNA 和yRNA 片段。这些细胞外 sRNA (ex-sRNA) 由许多不同的细胞类型包装和分泌。 Ex-sRNA 在多种疾病背景下表现出丰度差异,因此被提议作为非常合适的生物标志物。此外,据报道,外泌体携带的 ex-sRNA 可在接收细胞中引发生理反应。尽管存在争议,但源自植物和微生物的外源 ex-sRNA 也已在人类血液中得到描述。该领域仍有待最终解决的基本问题涉及(i)人体体液中外源ex-sRNA的存在和机制来源,(ii)人体循环中ex-sRNA的检测和测量,(iii)ex-sRNA输出和输入的选择性,(iv)ex-sRNA递送至细胞靶点的敏感性和特异性,以及(v)细胞、组织、器官和生物体范围的影响 ex-sRNA。我们将在这篇评论中调查大多数这些问题的知识现状。
Various biotypes of endogenous small RNAs (sRNAs) have been detected in human circulation including microRNAs, tRNA, rRNA and yRNA fragments. These extracellular sRNAs (ex-sRNAs) are packaged and secreted by many different cell types. Ex-sRNAs exhibit differences in abundance in several disease contexts and have therefore been proposed as well-suited biomarkers. Furthermore, exosome-borne ex-sRNAs have been reported to elicit physiological responses in receiving cells. Albeit controversial, exogenous ex-sRNAs derived from plants and microorganisms have also been described in human blood. Essential questions which remain to be conclusively addressed in the field concern the (i) presence and mechanistic sources of exogenous ex-sRNA in human bodily fluids, (ii) detection and measurement of ex-sRNA in human circulation, (iii) selectivity of ex-sRNA export and import, (iv) sensitivity and specificity of ex-sRNA delivery to cellular targets, and (v) cell-, tissue-, organ- and organism-wide impacts of ex-sRNAs. We will survey the present state of knowledge of most of these questions in this review.