Gene Symbol: TNRC6C
Description: trinucleotide repeat containing 6C
Alias: trinucleotide repeat-containing gene 6C protein
Species: human
Products:     TNRC6C

Top Publications

  1. Chen C, Zheng D, Xia Z, Shyu A. Ago-TNRC6 triggers microRNA-mediated decay by promoting two deadenylation steps. Nat Struct Mol Biol. 2009;16:1160-6 pubmed publisher
    ..When tethered to mRNAs, all four human Ago proteins and TNRC6C are each able to recapitulate the two deadenylation steps...
  2. Huntzinger E, Braun J, Heimstädt S, Zekri L, Izaurralde E. Two PABPC1-binding sites in GW182 proteins promote miRNA-mediated gene silencing. EMBO J. 2010;29:4146-60 pubmed publisher
    ..In Drosophila melanogaster (Dm) GW182 and a human (Hs) orthologue, TNRC6C, the SD was previously shown to interact with the cytoplasmic poly(A)-binding protein (PABPC1)...
  3. Huntzinger E, Kuzuoğlu Öztürk D, Braun J, Eulalio A, Wohlbold L, Izaurralde E. The interactions of GW182 proteins with PABP and deadenylases are required for both translational repression and degradation of miRNA targets. Nucleic Acids Res. 2013;41:978-94 pubmed publisher
    ..melanogaster and human cells indicate that miRNA-mediated translational repression and degradation are mechanistically linked and are triggered through the interactions of GW182 proteins with PABP and deadenylases. ..
  4. Lazzaretti D, Tournier I, Izaurralde E. The C-terminal domains of human TNRC6A, TNRC6B, and TNRC6C silence bound transcripts independently of Argonaute proteins. RNA. 2009;15:1059-66 pubmed publisher
    ..Vertebrate genomes encode three GW182 paralogs (TNRC6A, TNRC6B, and TNRC6C), which may be functionally redundant...
  5. Fabian M, Mathonnet G, Sundermeier T, Mathys H, Zipprich J, Svitkin Y, et al. Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-dependent deadenylation. Mol Cell. 2009;35:868-80 pubmed publisher
    ..Importantly, we present evidence that GW182, a core component of the miRISC, directly interacts with PABP via its C-terminal region and that this interaction is required for miRNA-mediated deadenylation...
  6. Fabian M, Cieplak M, Frank F, Morita M, Green J, Srikumar T, et al. miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT. Nat Struct Mol Biol. 2011;18:1211-7 pubmed publisher
    ..Thus, GW182 serves as both a platform that recruits deadenylases and as a deadenylase coactivator that facilitates the removal of the poly(A) tail by CCR4-NOT. ..
  7. Baillat D, Shiekhattar R. Functional dissection of the human TNRC6 (GW182-related) family of proteins. Mol Cell Biol. 2009;29:4144-55 pubmed publisher
    ..Here, we describe the isolation and functional characterization of TNRC6B- and TNRC6C-containing complexes...
  8. Jinek M, Fabian M, Coyle S, Sonenberg N, Doudna J. Structural insights into the human GW182-PABC interaction in microRNA-mediated deadenylation. Nat Struct Mol Biol. 2010;17:238-40 pubmed publisher
    ..Here we show that a conserved motif in the human GW182 paralog TNRC6C interacts with the C-terminal domain of polyadenylate binding protein 1 (PABC) and present the crystal structure ..
  9. Braun J, Huntzinger E, Fauser M, Izaurralde E. GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA targets. Mol Cell. 2011;44:120-33 pubmed publisher

More Information


  1. Chekulaeva M, Mathys H, Zipprich J, Attig J, Colic M, Parker R, et al. miRNA repression involves GW182-mediated recruitment of CCR4-NOT through conserved W-containing motifs. Nat Struct Mol Biol. 2011;18:1218-26 pubmed publisher
  2. Zipprich J, Bhattacharyya S, Mathys H, Filipowicz W. Importance of the C-terminal domain of the human GW182 protein TNRC6C for translational repression. RNA. 2009;15:781-93 pubmed publisher
    ..In contrast to a single GW182 protein in Drosophila, the three GW182 paralogs TNRC6A, TNRC6B, and TNRC6C are encoded in mammalian genomes...
  3. Kozlov G, Safaee N, Rosenauer A, Gehring K. Structural basis of binding of P-body-associated proteins GW182 and ataxin-2 by the Mlle domain of poly(A)-binding protein. J Biol Chem. 2010;285:13599-606 pubmed publisher
    ..we report the crystal structures of the C-terminal Mlle (or PABC) domain in complex with peptides from GW182 (TNRC6C) and Ataxin-2...
  4. Kalantari R, Hicks J, Li L, Gagnon K, Sridhara V, Lemoff A, et al. Stable association of RNAi machinery is conserved between the cytoplasm and nucleus of human cells. RNA. 2016;22:1085-98 pubmed publisher
    ..Interactions with TRNC6A, TRNC6B, TNRC6C, and AGO3 are conserved between nuclei and cytoplasm...
  5. Schneider M, Najand N, Chaker S, Pare J, Haskins J, Hughes S, et al. Gawky is a component of cytoplasmic mRNA processing bodies required for early Drosophila development. J Cell Biol. 2006;174:349-58 pubmed
    ..This suggests that gw represents a previously unknown member of a small group of genes that need to be expressed zygotically during early embryo development...
  6. Guo H, Kazadaeva Y, Ortega F, Manjunath N, Desai T. Trinucleotide repeat containing 6c (TNRC6c) is essential for microvascular maturation during distal airspace sacculation in the developing lung. Dev Biol. 2017;430:214-223 pubmed publisher
    ..However, the majority of TNRC6b and all TNRC6c mutants die within 24h after birth, the latter with respiratory failure...
  7. Zekri L, Kuzuoğlu Öztürk D, Izaurralde E. GW182 proteins cause PABP dissociation from silenced miRNA targets in the absence of deadenylation. EMBO J. 2013;32:1052-65 pubmed publisher
    ..Our findings indicate that the recruitment of the CCR4-NOT complex by GW182 proteins releases PABP from the mRNA poly(A) tail, thereby disrupting mRNA circularization and facilitating translational repression and deadenylation. ..
  8. Chen Y, Boland A, Kuzuoğlu Öztürk D, Bawankar P, Loh B, Chang C, et al. A DDX6-CNOT1 complex and W-binding pockets in CNOT9 reveal direct links between miRNA target recognition and silencing. Mol Cell. 2014;54:737-50 pubmed publisher
    ..Together, our data provide the missing physical links in a molecular pathway that connects miRNA target recognition with translational repression, deadenylation, and decapping. ..
  9. Zielezinski A, Karlowski W. Early origin and adaptive evolution of the GW182 protein family, the key component of RNA silencing in animals. RNA Biol. 2015;12:761-70 pubmed publisher
    ..Our results indicate that a single-copy GW182/TNRC6C progenitor gene arose with the emergence of multicellularity and it multiplied in the last common ancestor of ..
  10. Huang K, Chadee A, Chen C, Zhang Y, Shyu A. Phosphorylation at intrinsically disordered regions of PAM2 motif-containing proteins modulates their interactions with PABPC1 and influences mRNA fate. RNA. 2013;19:295-305 pubmed publisher
    ..results indicate that changing the extent of phosphorylation of three PAM2-containing proteins (Tob2, Pan3, and Tnrc6c) alters their ability to interact with PABPC1...