Tissue specific expression of sialic acid metabolic pathway: role in GNE myopathy
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ORIGINAL PAPER
Tissue specific expression of sialic acid metabolic pathway: role in GNE myopathy Kapila Awasthi1 · Alok Srivastava2,3 · Sudha Bhattacharya4 · Alok Bhattacharya4 Received: 17 June 2020 / Accepted: 30 September 2020 © Springer Nature Switzerland AG 2020
Abstract GNE myopathy is an adult-onset degenerative muscle disease that leads to extreme disability in patients. Biallelic mutations in the rate-limiting enzyme UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine-kinase (GNE) of sialic acid (SA) biosynthetic pathway, was shown to be the cause of this disease. Other genetic disorders with muscle pathology where defects in glycosylation are known. It is yet not clear why a defect in SA biosynthesis and glycosylation affect muscle cells selectively even though they are ubiquitously present in all tissues. Here we have comprehensively examined the complete SA metabolic pathway involving biosynthesis, sialylation, salvage, and catabolism. To understand the reason for tissuespecific phenotype caused by mutations in genes of this pathway, we analysed the expression of different SA pathway genes in various tissues, during the muscle tissue development and in muscle tissues from GNE myopathy patients (p.Met743Thr) using publicly available databases. We have also analysed gene co-expression networks with GNE in different tissues as well as gene interactions that are unique to muscle tissues only. The results do show a few muscle specific interactions involving ANLN, MYO16 and PRAMEF25 that could be involved in specific phenotype. Overall, our results suggest that SA biosynthetic and catabolic genes are expressed at a very low level in skeletal muscles that also display a unique gene interaction network. Keywords Sialic acid · Glycoconjugates · GNE myopathy · Sialic acid metabolic pathway · Neuromuscular disorder · Skeletal muscles
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10974-020-09590-7) contains supplementary material, which is available to authorized users. * Alok Bhattacharya [email protected] Kapila Awasthi [email protected] Alok Srivastava [email protected] Sudha Bhattacharya [email protected] 1
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
2
Amity Institute of Integrative Sciences and Health, Amity University Haryana, Amity Education Valley, Gurgaon, India
3
Institute of Bioinformatics and Computational Biology, Visakhapatnam, Andhra Pradesh, India
4
Ashoka University, Plot No. 2, Rajiv Gandhi Education City, P.O.Rai, Sonepat, Haryana 131029, India
A large number of proteins and lipids display extensive glycosylation involving several different sugar groups such as mannose, glucose, galactose, fucose, and SA at multiple sites. The main types of protein glycosylation in humans include N-, O-linked glycans, phosphorylated glycans, glycosaminoglycan (GAG), and glypiation (GPI anchor attachment) whereas glycosphingolipids make up the majority of glycoconjugates in lipi
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