Structural characterisation of TNRC6A nuclear localisation signal in complex with importin-alpha

• Published in: PloS one Vol. 12; no. 8; p. e0183587
• Main Authors: Chaston, Jessica J, Stewart, Alastair Gordon, Christie, Mary
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24-08-2017; Public Library of Science (PLoS)
• Subjects: alpha Karyopherins - metabolism; Antigens; Autoantigens - classification; Autoantigens - metabolism; Binding sites; Biology and life sciences; Crystallography, X-Ray; Degradation; Gene expression; Humans; Localization; Machinery and equipment; Medicine and Health Sciences; MicroRNA; miRNA; Molecular biology; mRNA; mRNA turnover; Nuclear Localization Signals; Nuclear transport; Phosphorylation; Physical Sciences; Protein Binding; Protein Conformation; Protein transport; Proteins; Receptors; Research and Analysis Methods; Ribonucleic acid; RNA; RNA-Binding Proteins - classification; RNA-Binding Proteins - metabolism; Scaffolds; Translocation; Australia; New South Wales Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0183587

The GW182/TNRC6 family of proteins are central scaffolds that link microRNA-associated Argonaute proteins to the cytoplasmic decay machinery for targeted mRNA degradation processes. Although nuclear roles for the GW182/TNRC6 proteins are unknown, recent reports have demonstrated nucleocytoplasmic shuttling activity that utilises the importin-α and importin-β transport receptors for nuclear translocation. Here we describe the structure of mouse importin-α in complex with the TNRC6A nuclear localisation signal peptide. We further show that the interactions observed between TNRC6A and importin-α are conserved between mouse and human complexes. Our results highlight the ability of monopartite cNLS sequences to maximise contacts at the importin-α major binding site, as well as regions outside the main binding cavities.