RNA-Binding Proteins in the Post-transcriptional Control of Skeletal Muscle Development, Regeneration and Disease

Abstract

Embryonic myogenesis is a temporally and spatially regulated process that generates skeletal muscle of the trunk and limbs. During this process, mononucleated myoblasts derived from myogenic progenitor cells within the somites undergo proliferation, migration and differentiation to elongate and fuse into multinucleated functional myofibers. Skeletal muscle is the most abundant tissue of the body and has the remarkable ability to self-repair by re-activating the myogenic program in muscle stem cells, known as satellite cells. Post-transcriptional regulation of gene expression mediated by RNA-binding proteins is critically required for muscle development during embryogenesis and for muscle homeostasis in the adult. Differential subcellular localization and activity of RNA-binding proteins orchestrates target gene expression at multiple levels to regulate different steps of myogenesis. Dysfunctions of these post-transcriptional regulators impair muscle development and homeostasis, but also cause defects in motor neurons or the neuromuscular junction, resulting in muscle degeneration and neuromuscular disease. Many RNA-binding proteins, such as members of the muscle blind-like (MBNL) and CUG-BP and ETR-3-like factors (CELF) families, display both overlapping and distinct targets in muscle cells. Thus they function either cooperatively or antagonistically to coordinate myoblast proliferation and differentiation. Evidence is accumulating that the dynamic interplay of their regulatory activity may control the progression of myogenic program as well as stem cell quiescence and activation. Moreover, the role of RNA-binding proteins that regulate post-transcriptional modification in the myogenic program is far less understood as compared with transcription factors involved in myogenic specification and differentiation. Here we review past achievements and recent advances in understanding the functions of RNA-binding proteins during skeletal muscle development, regeneration and disease, with the aim to identify the fundamental questions that are still open for further investigations.

A Mesp1-dependent developmental breakpoint in transcriptional and epigenomic specification of early cardiac precursors

“…3D). Mesp1 KO cells of the Mesp1ME upregulated posterior mesoderm organization genes ( Fgf10 and Gsc ) (Probst et al, 2020; Meijer et al, 2000; Branney et al, 2009) and the non-cardiac mesoderm gene Anxa2 (Schwartz et al, 2014; Wang et al, 2015), and downregulated Lefty2, Rac1 , and myogenesis differentiation gene Pcbp1 (Shi & Grifone, 2021) (Fig. 3J, Table S4H).…”

Integrative analysis of macrophage ribo-Seq and RNA-Seq data define glucocorticoid receptor regulated inflammatory response genes into distinct regulatory classes

“…For example, acute inflammatory responses may be suppressed by the rapid mRNA transcript degradation of cytokines, chemokines, enzymes, and other mediators [99] . Such post-transcriptional regulation is orchestrated by a diverse group of regulatory factors including RNA-binding proteins (RBP), microRNAs (miRNA) and other classes of small noncoding RNAs (sncRNA), which recognize and bind to sequences present in their target mRNAs [100] , [101] , [102] . Next generation sequencing methods such as RNA-seq, combined with ribo-seq, offers a quantitative approach to determine and understand the transcriptional and post-transcriptional gene regulation networks that GR acts within.…”

RNA-Binding Proteins in the Regulation of Adipogenesis and Adipose Function

“…RBPs play key roles in fundamental cellular activities, including proliferation, differentiation, and apoptosis. Dysregulation of RBPs leads to a variety of diseases, such as cancer [ 28 ], myopathies [ 29 , 30 ], and neurological [ 31 ] diseases. Although a large number of RBPs have been identified to mediate RNA metabolism, only a few of them have been studied in adipose tissue.…”