Human TNRC6A is an Argonaute-navigator protein for microRNA-mediated gene silencing in the nucleus.

Authors :: Nishi K
Nishi A
Nagasawa T
Ui-Tei K
Source :: RNA (New York, N.Y.) [RNA] 2013 Jan; Vol. 19 (1), pp. 17-35. Date of Electronic Publication: 2012 Nov 13.
Publication Year :: 2013
Abstract: GW182 family proteins play important roles in microRNA (miRNA)-mediated gene silencing. They interact with Argonaute (Ago) proteins and localize in processing bodies, which are cytoplasmic foci involved in mRNA degradation and storage. Here, we demonstrated that human GW182 paralog, TNRC6A, is a nuclear-cytoplasmic shuttling protein, and its subcellular localization is conducted by a nuclear export signal (NES) and a nuclear localization signal (NLS) identified in this study. TNRC6A with mutations in its NES region was predominantly localized in the nucleus in an Ago-independent manner. However, it was found that TNRC6A could bring Ago protein into the nucleus via its Ago-interacting motif(s). Furthermore, miRNAs were also colocalized with nuclear TNRC6A-Ago and exhibited gene silencing activity. These results proposed the possibility that TNRC6A plays an important role in navigating Ago protein into the nucleus to lead miRNA-mediated gene silencing.

Subjects :: Amino Acid Motifs
Autoantigens genetics
Cell Nucleus genetics
HeLa Cells
Humans
Mutation
Nuclear Export Signals genetics
Nuclear Export Signals physiology
Nuclear Localization Signals genetics
Nuclear Localization Signals metabolism
Nucleocytoplasmic Transport Proteins metabolism
RNA-Binding Proteins genetics
Argonaute Proteins metabolism
Autoantigens metabolism
Cell Nucleus metabolism
Gene Silencing
MicroRNAs metabolism
RNA-Binding Proteins metabolism

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