Identification of proteins that bind extracellular microRNAs secreted by the parasitic nematode Trichinella spiralis.

Identification of proteins that bind extracellular microRNAs secreted by the parasitic nematode Trichinella spiralis.
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DOI:
10.1242/bio.060096
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发表时间:
2023-11-15
期刊:
影响因子:
2.4
通讯作者:
--
中科院分区:
生物学4区
文献类型:
--
作者:

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小的非编码RNA如microRNA(miRNAs)在真核生物中是保守的,并且在调节基因表达中起关键作用。在许多生物体中,miRNA也从细胞分泌,通常包裹在囊泡如外来体中,有时在囊泡外。miRNA分泌的机制,它们如何在细胞外稳定以及它们的功能重要性知之甚少。最近,我们将寄生线虫旋毛虫作为研究miRNA分泌的模型。T.旋毛虫肌肉期幼虫(MSL)分泌大量的主要位于囊泡外的miRNA。在这里,我们调查了T. spiralis miRNAs在细胞外可能保持稳定。利用蛋白质组学技术,我们鉴定了T. spiralis幼虫,并表征了它们的RNA结合特性。一种是已知的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。另一种蛋白质可能是一种新的RNA结合蛋白,它与miRNA结合而不显示序列特异性。我们的研究结果提示T. spiralis,可能与更广泛地理解细胞外miRNA的生物学有关。摘要:寄生线虫旋毛虫分泌的microRNA不包含在细胞外囊泡中。在这里,我们发现并表征了两种可能参与稳定这些microRNA的蛋白质。
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. Summary: The parasitic nematode Trichinella spiralis secretes microRNAs that are not contained within extracellular vesicles. Here we discover and characterize two proteins that may be involved in stabilising these microRNAs.
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