Identification and Characterization of 1700029J07RIK, a Novel Gene Expressed in Skeletal Muscle

Abstract

Skeletal muscle atrophy is the loss of muscle mass that results from a wide range of conditions including denervation, corticosteroid exposure, and aging. 1700029J07RIK is a putative novel gene suggested to be involved in skeletal muscle atrophy. The 1700029J07RIK gene was found to be induced following denervation in mice and is differentially expressed in Muscle RING Finger 1 (MuRF1) knockout mice compared to wild‐type mice. A previous microarray analysis of muscle tissue isolated from wild‐type control mice and MuRF1 knockout mice revealed that the expression of the 1700029J07RIK gene is unchanged at 3 days post‐denervation, while expression is significantly induced in wild‐type mice at 14 days post denervation but remains unchanged in the MuRF1‐null animals. It has been well established that muscle cells go through a distinct developmental timeline in which they proliferate as single cell myoblasts and then differentiate and fuse into multinucleated myotubes. Quantitative PCR was used to confirm that the 1700029J07RIK gene is expressed in proliferating cells and increases in expression as muscle cells differentiate. To characterize the transcriptional regulation of 1700029J07RIK, promoter fragments were cloned into a reporter plasmid, transfected into muscle cells and found to have significant transcriptional activity, while ectopic expression of myogenic regulatory factors appear to modulate the activity of the 1700029J07RIK reporter genes. In addition, the 1700029J07RIK cDNA was cloned from muscle cells and fused with green fluorescent protein and visualized by confocal fluorescent microscopy revealing an interesting perinuclear and cytoplasmic localization of the 1700029J07RIK protein in muscle cells. Finally, it was observed that overexpression of 1700029J07RIK resulted in inhibition of muscle cell differentiation and attenuation of the ERK branch of the MAP Kinase signaling pathway. While there is virtually nothing known about this novel gene in the context of skeletal muscle, the results presented here suggest 1700029J07RIK may play a role in muscle cell differentiation and in the skeletal muscle atrophy cascade.Support or Funding InformationThe work was support by University of North Florida Transformational Learning Opportunity grants and a University of North Florida Foundation Board Grant to D.W.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.