MRC London Institute of Medical Sciences, Du Cane Road, London, W12 0NN, UK.
Department of Life Sciences, Imperial College London, SW7 2AZ, UK.
Biol Open. 2023 Nov 15;12(11). doi: 10.1242/bio.060096. Epub 2023 Nov 9.
Small non-coding RNAs such as microRNAs (miRNAs) are conserved across eukaryotes and play key roles in regulating gene expression. In many organisms, miRNAs are also secreted from cells, often encased within vesicles such as exosomes, and sometimes extravesicular. The mechanisms of miRNA secretion, how they are stabilised outside of cells and their functional importance are poorly understood. Recently, we characterised the parasitic nematode Trichinella spiralis as a model to study miRNA secretion. T. spiralis muscle-stage larvae (MSL) secrete abundant miRNAs which are largely extravesicular. Here, we investigated how T. spiralis miRNAs might remain stable outside of cells. Using proteomics, we identified two RNA binding proteins secreted by T. spiralis larvae and characterised their RNA binding properties. One, a homologue of the known RNA binding protein KSRP, binds miRNA in a selective and sequence-specific fashion. Another protein, which is likely a novel RNA binding protein, binds to miRNA without exhibiting sequence specificity. Our results suggest a possible mechanism for miRNA secretion by T. spiralis and may have relevance for understanding the biology of extracellular miRNA more widely.
小非编码 RNA 如 microRNAs (miRNAs) 在真核生物中是保守的,在调节基因表达中发挥关键作用。在许多生物体中,miRNAs 也从细胞中分泌出来,通常被包裹在囊泡中,如外泌体,有时也在囊泡外。miRNA 分泌的机制、它们在细胞外的稳定性以及它们的功能重要性还知之甚少。最近,我们将寄生线虫旋毛虫作为研究 miRNA 分泌的模型进行了研究。旋毛虫肌肉期幼虫 (MSL) 分泌大量的 miRNA,这些 miRNA 主要是囊外的。在这里,我们研究了旋毛虫 miRNA 如何在细胞外保持稳定。通过蛋白质组学,我们鉴定了两种由旋毛虫幼虫分泌的 RNA 结合蛋白,并对其 RNA 结合特性进行了表征。一种是已知 RNA 结合蛋白 KSRP 的同源物,以选择性和序列特异性的方式结合 miRNA。另一种蛋白可能是一种新的 RNA 结合蛋白,它与 miRNA 结合而没有表现出序列特异性。我们的结果为旋毛虫 miRNA 的分泌提出了一种可能的机制,可能对更广泛地理解细胞外 miRNA 的生物学具有重要意义。