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The mRNA Binding Proteome of Proliferating and Differentiated Muscle Cells

Genomics, Proteomics & Bioinformatics 2020年第4期18卷 384-396页

作者： Monika Hiller Miriam Geissler George Janssen Peter van Veelen Annemieke Aartsma-Rus pietro spitali Department of Human Genetics Leiden University Medical CenterLeiden 2333 ZCthe Netherlands Center for Proteomics and Metabolomics Leiden University Medical CenterLeiden 2333 ZCthe Netherlands

Muscle formation is a coordinated process driven by extensive gene expression changes where single cells fuse together to form multinucleated muscle fibers. Newly synthesized m RNAs 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.

关键词： RNA binding protein Interactome Duchenne muscular dystrophy Proteomics Skeletal muscle

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