Sarwade Rucha D, Khalique Abdul, Kulkarni Shardul D, Pandey Poonam R, Gaikwad Naina, Seshadri Vasudevan
National Centre of Cell Science, Ganeshkhind, Pune, 411007, India; Savitribai Phule Pune University, Ganeshkhind, Pune, 411007, India.
National Centre of Cell Science, Ganeshkhind, Pune, 411007, India.
Biochem Biophys Res Commun. 2020 Jun 4;526(3):618-625. doi: 10.1016/j.bbrc.2020.03.106. Epub 2020 Apr 2.
Glucose mediated insulin biosynthesis is tightly regulated and shared between insulin granule proteins such as its processing enzymes, prohormone convertases, PC1/3 and PC2. However, the molecular players involved in the co-ordinated translation remain elusive. The trans-acting factors like PABP (Poly A Binding Protein) and PDI (Protein Disulphide Isomerize) binds to a conserved sequence in the 5'UTR of insulin mRNA and regulates its translation. Here, we demonstrate that 5'UTR of PC1/3 and PC2 also associate with PDI and PABP. We show that a' and RRM 3-4 domains of PDI and PABP respectively, are necessary for RNA binding activity to the 5'UTRs of insulin and its processing enzymes.
葡萄糖介导的胰岛素生物合成受到严格调控，且在胰岛素颗粒蛋白（如其加工酶、激素原转化酶PC1/3和PC2）之间共享。然而，参与协同翻译的分子机制仍不清楚。像聚腺苷酸结合蛋白（PABP）和蛋白质二硫键异构酶（PDI）这样的反式作用因子会与胰岛素mRNA 5'非翻译区（5'UTR）中的保守序列结合，并调节其翻译。在这里，我们证明PC1/3和PC2的5'UTR也与PDI和PABP相关联。我们表明，PDI的α结构域和PABP的RRM 3-4结构域分别对于与胰岛素及其加工酶的5'UTR的RNA结合活性是必需的。
