Liu Xiao-Man, Halushka Marc K
The Stanley Center for Psychiatric Research, The Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts.
Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio.
Lab Invest. 2025 Feb;105(2):102206. doi: 10.1016/j.labinv.2024.102206. Epub 2024 Dec 6.
Over the past decade, a scientific field has been developed demonstrating microRNAs (miRNAs) to be actively sorted into extracellular vesicles via specific nucleotide motifs that interact with discrete RNA-binding proteins. These miRNAs are proposed to be transported into recipient cells in which they can regulate specific cellular pathways. This mechanism could have enormous potential in explaining how cells signal and regulate other cells nearby or at a distance. Tens of studies have built this theme of a regulated transport of miRNAs. However, some concerns exist about this field. Taken together, there are concerns of a lack of a consistent motif, RNA-binding protein, or preferential miRNA involved in this process. In this study, we provide an expert and extensive analysis of the field that makes the cases for and against an active sorting mechanism. We provide potential explanations on why there is a lack of agreement. Most importantly, we provide ideas on how to move this field forward with more rigor and reproducibility. It is hoped that by engaging in a scientific debate of the pros and cons of this field, more rigorous experiments can be performed to conclusively demonstrate this biological activity.
在过去十年中，一个科学领域得到了发展，证明微小RNA（miRNA）通过与离散的RNA结合蛋白相互作用的特定核苷酸基序被积极分选到细胞外囊泡中。这些miRNA被认为会被转运到受体细胞中，在那里它们可以调节特定的细胞途径。这种机制在解释细胞如何向附近或远处的其他细胞发出信号并进行调节方面可能具有巨大潜力。数十项研究构建了这种miRNA调控运输的主题。然而，该领域存在一些问题。总体而言，人们担心在这个过程中缺乏一致的基序、RNA结合蛋白或优先miRNA。在本研究中，我们对该领域进行了专业且广泛的分析，阐述了支持和反对主动分选机制的理由。我们对为何缺乏一致性提供了潜在解释。最重要的是，我们提出了如何使该领域更严谨且具可重复性地向前发展的思路。希望通过参与对该领域利弊的科学辩论，能够进行更严谨的实验以确凿证明这种生物学活性。
