RRC ID 40059
Author Nishi K, Nishi A, Nagasawa T, Ui-Tei K.
Title Human TNRC6A is an Argonaute-navigator protein for microRNA-mediated gene silencing in the nucleus.
Journal RNA
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.
Volume 19(1)
Pages 17-35
Published 2013-1
DOI 10.1261/rna.034769.112
PII rna.034769.112
PMID 23150874
PMC PMC3527724
MeSH Amino Acid Motifs Argonaute Proteins / metabolism* Autoantigens / genetics Autoantigens / metabolism* Cell Nucleus / genetics Cell Nucleus / metabolism* Gene Silencing* HeLa Cells Humans MicroRNAs / metabolism* 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 RNA-Binding Proteins / metabolism*
IF 4.49
Times Cited 38
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
DNA material pcDNA3.1-myc-GFP (RDB14213) pcDNA3.1-myc-GFP-TNRC6A (RDB14214) pcDNA3.1-myc-GFP-TNRC6A -NES-mut (RDB14215) pcDNA3.1-myc-GFP-TNRC6A -NLS-mut (RDB14216) pcDNA3.1-myc-GFP-TNRC6A -NLS/NES-mut (RDB14217) pcDNA5-FLAG/HA/SBP (RDB14218) pcDNA5-FLAG/HA/SBP-TNRC6A (RDB14219) pcDNA5-FLAG/HA/SBP-TNRC6A-NES-mut (RDB14220) pcDNA5-FLAG/HA/SBP-TNRC6A-NLS-mut (RDB14221) pcDNA5-FLAG/HA/SBP-TNRC6A-NES/NLS-mut (RDB14222) pcDNA3.1-myc-GFP-TNRC6A-del.GW-I (RDB14223) pcDNA3.1-myc-GFP-TNRC6A-del.GW-II (RDB14224) pcDNA3.1-myc-GFP-TNRC6A-del.GW-III (RDB14225) pcDNA3.1-myc-GFP-TNRC6A-del.GW-I+II (RDB14226) pcDNA3.1-myc-GFP-TNRC6A-del.GW-I+III (RDB14227) pcDNA3.1-myc-GFP-TNRC6A-del.GW-II+III (RDB14228) pcDNA3.1-myc-GFP-TNRC6A-del.GW-I+II+III (RDB14229) pcDNA3.1-myc-GFP-TNRC6A-del.GW-I-NES-mut (RDB14230) pcDNA3.1-myc-GFP-TNRC6A-del.GW-II-NES-mut (RDB14231) pcDNA3.1-myc-GFP-TNRC6A-del.GW-I+II-NES-mut (RDB14232) pcDNA3.1-myc-GFP-TNRC6A-del.GW-I+III-NES-mut (RDB14233) pcDNA3.1-myc-GFP-TNRC6A-del.GW-II+III-NES-mut (RDB14234) pcDNA3.1-myc-GFP-TNRC6A-del.GW-I+II+III-NES-mut (RDB14235) pSUPER-retro-puro-DsRed (RDB14240) pSUPER-retro-puro-CXCR4 (RDB14241) psiCHECK1-CXCR4 (RDB14242).