The emerging role of E3 ubiquitin ligase RNF213 as an antimicrobial host determinant

Front Cell Infect Microbiol. 2023 Aug 15:13:1205355. doi: 10.3389/fcimb.2023.1205355. eCollection 2023.

Abstract

Ring finger protein 213 (RNF213) is a large E3 ubiquitin ligase with a molecular weight of 591 kDa that is associated with moyamoya disease, a rare cerebrovascular disease. It is located in the cytosol and perinuclear space. Missense mutations in this gene have been found to be more prevalent in patients with moyamoya disease compared with that in healthy individuals. Understanding the molecular function of RNF213 could provide insights into moyamoya disease. RNF213 contains a C3HC4-type RING finger domain with an E3 ubiquitin ligase domain and six AAA+ adenosine triphosphatase (ATPase) domains. It is the only known protein with both AAA+ ATPase and ubiquitin ligase activities. Recent studies have highlighted the role of RNF213 in fighting against microbial infections, including viruses, parasites, bacteria, and chlamydiae. This review aims to summarize the recent research progress on the mechanisms of RNF213 in pathogenic infections, which will aid researchers in understanding the antimicrobial role of RNF213.

Keywords: RNF213; antimicrobial infection; cell autonomous immunity; lipid droplets; ubiquitination.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases
  • Anti-Infective Agents*
  • Genes, Regulator
  • Humans
  • Moyamoya Disease*
  • Transcription Factors
  • Ubiquitin-Protein Ligases

Substances

  • Ubiquitin-Protein Ligases
  • Transcription Factors
  • Anti-Infective Agents
  • Adenosine Triphosphatases
  • RNF213 protein, human

Supplementary concepts

  • Moyamoya disease 1

Grants and funding

This work was supported by grants from National Natural Science Foundation of China (82272306 and 82072270), College Students Innovation and Entrepreneurship Training Program of Shandong First Medical University (2022104391291), National College Students’ Innovation and Entrepreneurship Training Program (202210439002), Taishan Scholars Program (tstp20221142), and Academic Promotion Programme of Shandong First Medical University (2019LJ001).