RC3H2

Description

The RC3H2 (ring finger and CCCH-type domains 2) is a protein-coding gene located on chromosome 9.

RC3H2 is a protein that plays a role in post-transcriptional regulation of gene expression. It is involved in the suppression of several immune response genes, including ICOS, TNFRSF4, and TNF. RC3H2 also interacts with the microRNA processing pathway and acts as a ubiquitin E3 ligase.

RC3H2 is a post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR. It binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs. In follicular helper T (Tfh) cells, RC3H2 represses ICOS and TNFRSF4 expression, preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity. In resting or LPS-stimulated macrophages, RC3H2 controls inflammation by suppressing TNF expression. RC3H2 also recognizes CDE in its own mRNA and in that of paralogous RC3H1, possibly leading to feedback loop regulation. It is a miRNA-binding protein that regulates microRNA homeostasis. RC3H2 enhances DICER-mediated processing of pre-MIR146a but reduces mature MIR146a levels through an increase of 3' end uridylation. Both RC3H2 and miRNAs may act together to inhibit ICOS mRNA expression. RC3H2 acts as a ubiquitin E3 ligase, pairing with E2 enzymes UBE2B, UBE2D2, UBE2E2, UBE2E3, UBE2G2, UBE2K and UBE2Q2 and producing polyubiquitin chains. RC3H2 shows the strongest activity when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2 complexes and generate both short and long polyubiquitin chains. It is involved in the ubiquitination of MAP3K5. RC3H2 is able to interact with double-stranded RNA (dsRNA). It interacts with EDC4 and the CCR4-NOT deadenylase complex. RC3H2 interacts with MAP3K5; this interaction is probably stimulus-dependent.

RC3H2 is also known as MNAB, RNF164.

Associated Diseases

WES Whole Exome Sequencing