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Bta-miR-206 和一种新型 lncRNA-lncA2B1 通过共同结合蛋白 HNRNPA2B1 促进骨骼肌卫星细胞的成肌分化。

Bta-miR-206 and a Novel lncRNA-lncA2B1 Promote Myogenesis of Skeletal Muscle Satellite Cells via Common Binding Protein HNRNPA2B1.

机构信息

Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, Tianjin 300384, China.

College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300384, China.

出版信息

Cells. 2023 Mar 27;12(7):1028. doi: 10.3390/cells12071028.

DOI:10.3390/cells12071028
PMID:37048101
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10093610/
Abstract

Skeletal muscle satellite cells (MuSCs) can proliferate, differentiate, and self-renew, and can also participate in muscle formation and muscle injury repair. Long noncoding RNAs (lncRNAs) can play an important role with the RNA binding protein and microRNAs (miRNAs) to regulate the myogenesis of bovine MuSCs, however, its molecular mechanism is still being explored. In this study, differentially expressed 301 lncRNAs were identified during the myogenic differentiation of cells based on an in vitro model of induced differentiation of bovine MuSCs using RNA sequencing (RNA-seq). Based on the ability of miR-206 to regulate myogenic cell differentiation, a new kind of lncRNA-lncA2B1 without protein-coding ability was found, which is expressed in the nucleus and cytoplasm. Subsequently, lncA2B1 inhibited cell proliferation by downregulating the expression of the proliferation marker Pax7 and promoted myogenic differentiation by upregulating the expression of the differentiation marker MyHC, whose regulatory function is closely related to miR-206. By RNA pulldown/LC-MS experiments, heterogeneous ribonucleoprotein A2/B1 (HNRNPA2B1), and DExH-Box Helicase 9 (DHX9) were identified as common binding proteins of lncA2B1 and miR-206. Overexpression of lncA2B1 and miR-206 significantly upregulated the expression level of HNRNPA2B1. Downregulation of HNRNPA2B1 expression significantly decreased the expression level of the differentiation marker MyHC, which indicates that miR-206 and lncA2B1 regulate myogenic differentiation of bovine MuSCs by acting on HNRNPA2B1. This study screened and identified a novel lncRNA-lncA2B1, which functions with miR-206 to regulate myogenesis via the common binding proteins HNRNPA2B1. The results of this study provide a new way to explore the molecular mechanisms by which lncRNAs and miRNAs regulate muscle growth and development.

摘要

骨骼肌卫星细胞 (MuSCs) 可以增殖、分化和自我更新,还可以参与肌肉形成和肌肉损伤修复。长链非编码 RNA (lncRNA) 可以与 RNA 结合蛋白和 microRNAs (miRNAs) 一起发挥重要作用,调节牛 MuSCs 的肌发生,但它的分子机制仍在探索中。在这项研究中,基于牛 MuSCs 诱导分化的体外模型,使用 RNA 测序 (RNA-seq) ,鉴定了细胞肌发生分化过程中差异表达的 301 个 lncRNA。基于 miR-206 调节肌细胞分化的能力,发现了一种新的无蛋白编码能力的 lncRNA-lncA2B1,它在核和细胞质中表达。随后,lncA2B1 通过下调增殖标志物 Pax7 的表达抑制细胞增殖,通过上调分化标志物 MyHC 的表达促进肌生成分化,其调节功能与 miR-206 密切相关。通过 RNA 下拉/LC-MS 实验,鉴定了异质核糖核蛋白 A2/B1 (HNRNPA2B1) 和 DExH-Box 解旋酶 9 (DHX9) 为 lncA2B1 和 miR-206 的共同结合蛋白。lncA2B1 和 miR-206 的过表达显著上调了 HNRNPA2B1 的表达水平。下调 HNRNPA2B1 的表达水平显著降低了分化标志物 MyHC 的表达水平,表明 miR-206 和 lncA2B1 通过作用于 HNRNPA2B1 调节牛 MuSCs 的肌生成。本研究筛选并鉴定了一种新的 lncRNA-lncA2B1,它与 miR-206 一起通过共同结合蛋白 HNRNPA2B1 调节肌发生。本研究结果为探索 lncRNA 和 miRNAs 调节肌肉生长和发育的分子机制提供了新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/cad26966c4a0/cells-12-01028-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/58fdc257063c/cells-12-01028-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/0ae73ecdfbff/cells-12-01028-g0A2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/77107d594f85/cells-12-01028-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/da6040a2b252/cells-12-01028-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/6daae5779db8/cells-12-01028-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/b80e88f3098f/cells-12-01028-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/30798f4e6e23/cells-12-01028-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/4b83e9016117/cells-12-01028-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/cad26966c4a0/cells-12-01028-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/58fdc257063c/cells-12-01028-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/0ae73ecdfbff/cells-12-01028-g0A2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/77107d594f85/cells-12-01028-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/da6040a2b252/cells-12-01028-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/6daae5779db8/cells-12-01028-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/b80e88f3098f/cells-12-01028-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/30798f4e6e23/cells-12-01028-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/4b83e9016117/cells-12-01028-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf6/10093610/cad26966c4a0/cells-12-01028-g007.jpg

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