Navigating translational control of gene expression in satellite cells

Abstract

Satellite cells, named for their satellite position around the sarcolemma of the myofibre, are responsible for skeletal muscle regeneration. Satellite cells normally reside in a quiescent state, but rapidly activate the myogenic program and the cell cycle in response to injury. Translational control of gene expression has emerged as an important regulator of satellite cell activity. Quiescent satellite cells maintain low levels of protein synthesis and selectively translate specific mRNAs to conserve limited energy. Activated satellite cells rapidly restore global protein synthesis to meet the demands of proliferating myogenic progenitors that participate in muscle repair. We propose a model by which translational control enables rapid protein level changes in response to injury-induced environmental shifts, serving as both a brake mechanism during quiescence and an accelerator for injury response. In this Chapter, we navigate the processing, translation and metabolism of newly transcribed mRNAs. We review the modifications of mRNA that occur during mRNA processing in the nucleus of satellite cells, and illustrate how these modifications impact the translation and stability of mRNAs. In the cytoplasm, we review how pathways work in concert to regulate protein synthesis globally, while trans acting microRNAs and RNA binding proteins modify specific mRNA translation within a context of tightly regulated protein synthesis. While navigating translational control of gene expression in satellite cells, this chapter reveals that despite significant progress, the field remains nascent in the broader scope of translational control in cell biology. We propose that future investigations will benefit from incorporating emerging global analyses to study translational control of gene expression in rare satellite cells, and we pose unanswered questions that warrant future exploration.

Keywords: RNA binding proteins; Satellite cell; Stress granules and P bodies; Translation; eIF2α phosphorylation; mRNA processing; mTOR signaling; microRNA.