Department of Human Genetics, Leiden University Medical Center, Leiden 2333 ZC, the Netherlands.
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden 2333 ZC, the Netherlands.
Genomics Proteomics Bioinformatics. 2020 Aug;18(4):384-396. doi: 10.1016/j.gpb.2020.06.004. Epub 2020 Dec 16.
Muscle formation is a coordinated process driven by extensive gene expression changes where single cells fuse together to form multinucleated muscle fibers. Newly synthesized mRNAs are then regulated by RNA binding proteins (RBPs), affecting post-transcriptional transcript metabolism. Here, we determined how large-scale gene expression changes affect the catalog of RBPs by studying proliferating and differentiated muscle cells in healthy and dystrophic conditions. Transcriptomic analysis showed that the expression of more than 7000 genes was affected during myogenesis. We identified 769 RBPs, of which 294 were muscle-specific and 49 were uniquely shared with cardiomyocytes. A subset of 32 RBPs (half of which were muscle-specific) was found to be preferentially associated with target mRNAs in either myoblasts (MBs) or myotubes (MTs). A large proportion of catalytic proteins were bound to mRNAs even though they lack classical RNA binding domains. Finally, we showed how the identification of cell-specific RBPs enabled the identification of biomarkers that can separate healthy individuals from dystrophic patients. Our data show how interactome data can shed light on new basic RNA biology as well as provide cell-specific data that can be used for diagnostic purposes.
肌肉形成是一个由广泛的基因表达变化驱动的协调过程，其中单个细胞融合在一起形成多核肌纤维。新合成的 mRNA 然后被 RNA 结合蛋白 (RBPs) 调节，影响转录后转录物代谢。在这里，我们通过研究健康和萎缩条件下增殖和分化的肌肉细胞，确定了大规模基因表达变化如何影响 RBP 的目录。转录组分析显示，在肌发生过程中，超过 7000 个基因的表达受到影响。我们鉴定了 769 个 RBPs，其中 294 个是肌肉特异性的，49 个是与心肌细胞特有的。发现 32 个 RBP 亚组（其中一半是肌肉特异性的）优先与成肌细胞 (MB) 或肌管 (MT) 中的靶 mRNA 结合。尽管缺乏经典的 RNA 结合域，但很大一部分催化蛋白仍与 mRNA 结合。最后，我们展示了如何识别细胞特异性 RBPs 能够鉴定出可将健康个体与萎缩症患者区分开来的生物标志物。我们的数据表明，互作组数据如何能够揭示新的基本 RNA 生物学，并提供可用于诊断目的的细胞特异性数据。
