Origin and evolution of TRIM proteins: new insights from the complete TRIM repertoire of zebrafish and pufferfish.

Pierre Boudinot,Pierre Pontarotti,Louis Du Pasquier,Lieke M Van Der Aa,Abdenour Benmansour,Luc Jouneau,Jean-Pierre Levraud,Valérie Briolat,Nikolas Nikolaidis

doi:10.1371/journal.pone.0022022

Abstract

Tripartite motif proteins (TRIM) constitute a large family of proteins containing a RING-Bbox-Coiled Coil motif followed by different C-terminal domains. Involved in ubiquitination, TRIM proteins participate in many cellular processes including antiviral immunity. The TRIM family is ancient and has been greatly diversified in vertebrates and especially in fish. We analyzed the complete sets of trim genes of the large zebrafish genome and of the compact pufferfish genome. Both contain three large multigene subsets - adding the hsl5/trim35-like genes (hltr) to the ftr and the btr that we previously described - all containing a B30.2 domain that evolved under positive selection. These subsets are conserved among teleosts. By contrast, most human trim genes of the other classes have only one or two orthologues in fish. Loss or gain of C-terminal exons generated proteins with different domain organizations; either by the deletion of the ancestral domain or, remarkably, by the acquisition of a new C-terminal domain. Our survey of fish trim genes in fish identifies subsets with different evolutionary dynamics. trims encoding RBCC-B30.2 proteins show the same evolutionary trends in fish and tetrapods: they evolve fast, often under positive selection, and they duplicate to create multigenic families. We could identify new combinations of domains, which epitomize how new trim classes appear by domain insertion or exon shuffling. Notably, we found that a cyclophilin-A domain replaces the B30.2 domain of a zebrafish fintrim gene, as reported in the macaque and owl monkey antiretroviral TRIM5α. Finally, trim genes encoding RBCC-B30.2 proteins are preferentially located in the vicinity of MHC or MHC gene paralogues, which suggests that such trim genes may have been part of the ancestral MHC.

Highlights

The tripartite motif (TRIM) family – known as the Nterminal RING finger/B-box/coiled coil (RBCC) family– play major roles in development, tumor suppression, disease pathology and viral restriction/sensing [1,2]
The TRIM5a B30.2 domain binds the nucleocapsid of incoming viral particles and accelerates the uncoating of the viral core, while the RING/ B-box domains are essential for the localization in specific cytoplasmic ‘bodies’ [13,14,15] and mediate a TRIM5a higher-order self association that increases avidity for retroviral capsids [16,17]
Fish trim genes were named after the human orthologues, following the Ensembl annotations confirmed by the analysis of the domain organization of the protein

Summary

Introduction

The tripartite motif (TRIM) family – known as the Nterminal RING finger/B-box/coiled coil (RBCC) family– play major roles in development, tumor suppression, disease pathology and viral restriction/sensing [1,2]. This tripartite motif is associated with diverse C-terminal domains, which often determine the specificity of the interactions of TRIMs with other proteins. The Class IV TRIM proteins include multiple members involved in antiviral immunity at various levels of the interferon (IFN) signalling cascade. Ligand-binding loops of the TRIM5a B30.2 domain diversified during the evolution of primates, ensuring efficient restriction of specific retroviruses in the different species [18,19]. The specific modalities of these apparently independent multiplication and diversification events are still poorly understood

Methods

Results

Conclusion