Undergraduate Honors Theses

Thesis Defended

Spring 2019

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Molecular, Cellular, & Developmental Biology

First Advisor

Bradley Olwin

Abstract

Skeletal muscle is essential for our everyday mobility and has the unique ability to regenerate after injury through its resident muscle stem cells (MuSCs) (Frontera, Ochala 2015, Almeida et al., 2016). When the muscle is injured, its MuSCs transition to a myoblast cell fate, proliferate and fuse to each other and into injured muscle to create and repair skeletal muscle (Wang, Rudnicki, 2012).MuSCs express many new genes required for muscle formation that are challenging to transcribe, splice and translate into protein (Bland et al., 2010). We do not yet fully understand how nascent skeletal muscle regulates new mRNAs during muscle formation. However, we do know that regenerating and forming skeletal muscle expresses many RNA-binding proteins (RNABPs), which may regulate mRNA during myogenesis (Apponi et al., 2011, Keene et al. 2007). I sought to identify RNABPs that regulate mRNA and elucidate their function in skeletal muscle formation. I identified that the expression of the RNABP hnRNPA2B1 is up-regulated in the nuclei of MuSCs in a mouse model of skeletal muscle regeneration. Although hnRNPA2B1 is not necessary for skeletal muscle myoblast proliferation, it supports skeletal muscle differentiation and formation. Subsequently, I found that hnRNPA2B1 binds splicing machinery mRNA which then splice myogenic transcripts. These data indicate that hnRNPA2B1 regulates mRNA splicing to support skeletal muscle differentiation and formation. Further, these findings point towards RNABPs as regulators of mRNA stability and splicing during skeletal muscle differentiation.

Available for download on Sunday, April 11, 2021

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