Acute necrotizing encephalopathy-linked mutations in Nup358 impair interaction of Nup358 with TNRC6/GW182 and miRNA function

MicroRNA (miRNA)-mediated translational suppression of mRNAs is involved in the regulation of mul-tiple 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. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

Nup358 protein plays a role in coupling miRNA-induced silencing complex with target mRNA, and interacts with GW182 protein. Mutations in Nup358 associated with ANE1 may affect the miRNA pathway and contribute to the development of ANE1.