Mammals have three GW182 paralogues, TNRC6A, TNRC6B and TNRC6C. They interact directly with Argonaute (Ago) proteins and function downstream as effectors mediating mRNA repression. They repress mRNAs by recruiting the CCR4-NOT complex to the mRNA. They contain the N-terminal effector domain (NED), the middle Q-rich region, and the C-terminal effector domain (CED) containing the poly(A) binding protein (PABP)-interacting motif 2 (PAM2) and the RNA-recognition motif (RRM) [].This entry represents TNRC6C from vertebrates. Similar to TNRC6A/B, TNRC6C is essential for efficient miRNA repression [].
Trinucleotide repeat-containing gene 6C protein (TNRC6C) is one of three GW182 paralogs in mammalian genomes. It is enriched in P-bodies and important for efficient miRNA-mediated repression. TNRC6C is composed of an N-terminal glycine/tryptophan (G/W)-rich region containing an Ago hook responsible for Ago protein-binding; a ubiquitin-associated (UBA) domain and a glutamine (Q)-rich region in the middle region; a middle G/W-rich region, a RNA recognition motif (RRM), also called RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal G/W-rich region, at the C terminus. A bipartite C-terminal region including the middle and C-terminal G/W-rich regions is referred to as silencing domain, that triggers silencing of bound transcripts by inhibiting protein expression and promoting mRNA decay via deadenylation. The C-terminal half containing the RRM domain functions as a key effector domain mediating protein synthesis repression by TNRC6C [, ].
