Early origin and adaptive evolution of the GW182 protein family, the key component of RNA silencing in animals

RNA Biol. 2015;12(7):761-70. doi: 10.1080/15476286.2015.1051302.


The GW182 proteins are a key component of the miRNA-dependent post-transcriptional silencing pathway in animals. They function as scaffold proteins to mediate the interaction of Argonaute (AGO)-containing complexes with cytoplasmic poly(A)-binding proteins (PABP) and PAN2-PAN3 and CCR4-NOT deadenylases. The AGO-GW182 complexes mediate silencing of the target mRNA through induction of translational repression and/or mRNA degradation. Although the GW182 proteins are a subject of extensive experimental research in the recent years, very little is known about their origin and evolution. Here, based on complex functional annotation and phylogenetic analyses, we reveal 448 members of the GW182 protein family from the earliest animals to humans. 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 vertebrates in 2 rounds of whole genome duplication (WGD) resulting in 3 genes. Before the divergence of vertebrates, both the AGO- and CCR4-NOT-binding regions of GW182s showed significant acceleration in the accumulation of amino acid changes, suggesting functional adaptation toward higher specificity to the molecules of the silencing complex. We conclude that the silencing ability of the GW182 proteins improves with higher position in the taxonomic classification and increasing complexity of the organism. The first reconstruction of the molecular journey of GW182 proteins from the ancestral metazoan protein to the current mammalian configuration provides new insight into development of the miRNA-dependent post-transcriptional silencing pathway in animals.

Keywords: Argonaute; CCR4-NOT; GW-repeats; GW182; RNAi; TNRC6; WG/GW; gene silencing; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Evolution, Molecular*
  • Humans
  • Invertebrates / genetics
  • Invertebrates / metabolism
  • RNA Interference*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Vertebrates / genetics
  • Vertebrates / metabolism


  • Autoantigens
  • RNA-Binding Proteins
  • TNRC6A protein, human
  • TNRC6C protein, human