Ring finger and CCCH-type domains 2 (RC3H2)

Ring finger and CCCH-type domains 2 (RC3H2), also known as Roquin-2, is a highly conserved multi-domain protein. It features a RING finger domain conferring E3 ubiquitin ligase activity and a CCCH-type zinc finger domain that, together with a unique ROQ domain, mediates specific RNA binding. RC3H2 binds to conserved stem-loop motifs (constitutive decay elements or CDEs) in target mRNA 3'-untranslated regions, promoting deadenylation and degradation of these transcripts in a miRNA-independent manner. It plays a critical role in immune regulation by repressing the expression of key genes involved in T cell activation and inflammation (such as ICOS, TNFRSF4, TNF, and NFKBID), thus maintaining immunological self-tolerance and preventing hyperinflammatory states. RC3H2 acts as an E3 ubiquitin ligase, interacting with several E2 enzymes to assemble polyubiquitin chains and regulate substrate turnover. Dysfunction of RC3H2 or its paralog Roquin-1 is associated with autoimmunity, chronic inflammation, and potentially tumorigenesis. No clinically approved drugs are known to directly target RC3H2 as of the current knowledge. However, its central role in post-transcriptional gene regulation and immune homeostasis make it of interest as a potential therapeutic target for immune-related and inflammatory diseases.

Other names

Roquin-2MNABRNF164Membrane-associated nucleic acid-binding proteinRING finger and CCCH-type zinc finger domain-containing protein 2RING finger protein 164RING-type E3 ubiquitin transferase Roquin-2membrane-associated DNA binding proteinmembrane-associated nucleic acid-binding proteinring finger and CCCH-type zinc finger domains 2

Small molecules or biologics (in theory) that modulate RNA binding or E3 ligase activity could alter mRNA degradation pathways or immune responses