School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
Ashoka University, Plot No. 2, Rajiv Gandhi Education City, P.O.Rai, Sonepat, Haryana, 131029, India.
J Muscle Res Cell Motil. 2022 Jun;43(2):49-61. doi: 10.1007/s10974-022-09618-0. Epub 2022 May 7.
Mutations in the sialic acid biosynthesis enzyme GNE lead to a late-onset, debilitating neuromuscular disorder, GNE myopathy, characterized by progressive skeletal muscle weakness. The mechanisms responsible for skeletal muscle specificity, late-onset, and disease progression are unknown. Our main aim is to understand the reason for skeletal muscle-specific phenotype. To answer this question, we have analyzed the expression profile of the GNE gene and its multiple mRNA variants in different human tissues. A combinatorial approach encompassing bioinformatics tools and molecular biology techniques was used. NCBI, Ensembl, and GTEx were used for data mining. The expression analysis of GNE and its variants was performed with cDNA tissue panel using PCR and targeted RNA-seq. Among nine different GNE isoforms reported in this study, transcript variants 1, X1, and X2 were not tissue specific. Transcript variants 1, 6, X1, and X2, were found in skeletal muscles suggesting their possible role in GNE myopathy. In the current study, we present new data about GNE expression patterns in human tissues. Our results suggest that there may be a link between tissue-specific pathology and isoform pattern in skeletal muscles, which could provide clues for the development of new treatment strategies for GNE myopathy.
基因突变导致唾液酸生物合成酶 GNE 引起一种迟发性、进行性神经肌肉疾病，即 GNE 肌病，其特征为进行性骨骼肌无力。导致骨骼肌特异性、迟发性和疾病进展的机制尚不清楚。我们的主要目的是了解骨骼肌特异性表型的原因。为了回答这个问题，我们分析了 GNE 基因及其多种 mRNA 变体在不同人体组织中的表达谱。采用了包含生物信息学工具和分子生物学技术的组合方法。我们使用 NCBI、Ensembl 和 GTEx 进行数据挖掘。使用 cDNA 组织面板通过 PCR 和靶向 RNA-seq 对 GNE 及其变体的表达进行分析。在本研究中报道的 9 种不同的 GNE 异构体中，转录变体 1、X1 和 X2 没有组织特异性。在骨骼肌中发现了转录变体 1、6、X1 和 X2，提示它们可能在 GNE 肌病中发挥作用。在本研究中，我们提出了关于 GNE 在人体组织中表达模式的新数据。我们的结果表明，骨骼肌中的组织特异性病理学和异构体模式之间可能存在联系，这可能为 GNE 肌病的新治疗策略的发展提供线索。
