Deshmukh, P. and Singh, A. and Khuperkar, D. and Joseph , J. (0020) Acute necrotizing encephalopathy-linked mutations in Nup358 impair interaction of Nup358 with TNRC6/GW182 and miRNA function. Biochemical and Biophysical Research Communications., 559 (25). pp. 230-237. ISSN Volume 559, 25 June 2021, Pages 230-237

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Abstract

MicroRNA (miRNA)-mediated translational suppression of mRNAs is involved in the regulation of multiple cellular processes. A recent study showed that Nup358, a protein mutated in a neurological disorder called acute necrotizing encephalopathy 1 (ANE1), helps in the coupling of miRNA-induced silencing complex (miRISC) - consisting of miRNA, AGO and GW182/TNRC6 proteins - with the target mRNA. Here we provide a detailed characterization of the interaction between Nup358 and GW182. We identified that the N-terminal region of Nup358 directly interacts with the C-terminal silencing domain of GW182. Interestingly, ANE1-associated Nup358 mutants display reduced interaction with GW182. Consistent with this, one of the prevalent ANE1 mutations, 585th threonine (T) residue changed to methionine (M) [T585M] compromised Nup358's ability to function in the miRNA pathway. Collectively, these results suggest that the ANE1-associated mutations in Nup358 might affect the miRNA pathway and contribute to the development of ANE1.

Item Type:	Article
Subjects:	Cell Biology
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	22 Nov 2021 07:08
Last Modified:	22 Nov 2021 07:08
URI:	http://nccs.sciencecentral.in/id/eprint/1033

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