TRIM25 and its emerging RNA-binding roles in antiviral defense.

Nila Roy Choudhury,Gracjan Michlewski,Gregory Heikel

doi:10.1002/wrna.1588

Abstract

The innate immune system is the body's first line of defense against viruses, with pattern recognition receptors (PRRs) recognizing molecules unique to viruses and triggering the expression of interferons and other anti-viral cytokines, leading to the formation of an anti-viral state. The tripartite motif containing 25 (TRIM25) is an E3 ubiquitin ligase thought to be a key component in the activation of signaling by the PRR retinoic acid-inducible gene I protein (RIG-I). TRIM25 has recently been identified as an RNA-binding protein, raising the question of whether its RNA-binding activity is important for its role in innate immunity. Here, we review TRIM25's mechanisms and pathways in noninfected and infected cells. We also introduce models that explain how TRIM25 binding to RNA could modulate its functions and play part in the antiviral response. These findings have opened new lines of investigations into functional and molecular roles of TRIM25 and other E3 ubiquitin ligases in cell biology and control of pathogenic infections. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Interactions with Proteins and Other Molecules > Protein-RNA Recognition.

Highlights

Humans, as well as other organisms, must protect themselves from infection by viruses and other pathogens
It is unlikely that this would be sufficient to explain the differences in type I IFN induction seen due to the apparent redundancy of Tripartite Motif Containing 25 (TRIM25) in Retinoic AcidInducible Gene I Protein (RIG-I) signalling with other E3 ubiquitin ligases such as Riplet, TRIM4 and MEX3C66
TRIM25 plays an important role in innate immunity and has proven importance in inhibiting virus replication, the precise mechanisms are still unclear

Summary

Introduction

As well as other organisms, must protect themselves from infection by viruses and other pathogens. E3 ubiquitin ligase TRIM25 is newly identified RNA-binding protein which is emerging as a key factor in the innate immune response to RNA viruses. This may suggest that activation of full-length RIG-I signalling in response to viral RNA requires Riplet activity, but Riplet is redundant with the other E3 ubiquitin ligases in the ubiquitination of the RIG-I 2CARD alone.

Results

Conclusion