RC3H1 Antibody - #DF15706

Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF, TNFRSF4 and in many more mRNAs. Cleaves translationally inactive mRNAs harboring a stem-loop (SL), often located in their 3'-UTRs, during the early phase of inflammation in a helicase UPF1-independent manner (By similarity). Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs (By similarity). In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity (By similarity). In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression (By similarity). Also recognizes CDE in its own mRNA and in that of paralogous RC3H2, possibly leading to feedback loop regulation (By similarity). Recognizes and binds mRNAs containing a hexaloop stem-loop motif, called alternative decay element (ADE) (By similarity). Together with ZC3H12A, destabilizes TNFRSF4/OX40 mRNA by binding to the conserved stem loop structure in its 3'UTR (By similarity). Able to interact with double-stranded RNA (dsRNA). miRNA-binding protein that regulates microRNA homeostasis. Enhances DICER-mediated processing of pre-MIR146a but reduces mature MIR146a levels through an increase of 3' end uridylation. Both inhibits ICOS mRNA expression and they may act together to exert the suppression. Acts as a ubiquitin E3 ligase. Pairs with E2 enzymes UBE2A, UBE2B, UBE2D2, UBE2F, UBE2G1, UBE2G2 and UBE2L3 and produces polyubiquitin chains. Shows the strongest activity when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2 complexes and generate both short and long polyubiquitin chains.

Proteolytically cleaved after Arg-510 and Arg-579 by MALT1 in activated CD4(+) T cells; cleavage at Arg-510 and Arg-579 is critical for promoting RC3H1 degradation in response to T-cell receptor (TCR) stimulation, and hence is necessary for prolonging the stability of a set of mRNAs controlling Th17 cell differentiation.

Cytoplasm>P-body. Cytoplasmic granule.
Note: During stress, such as that induced by arsenite treatment, localizes to cytosolic stress granules (By similarity). Localization to stress granules, but not to P-bodies, depends upon the RING-type zinc finger (By similarity). ICOS repression may correlate with the localization to P-bodies, not to stress granules (By similarity).

Widely expressed. Expressed at higher level in cerebellum, spleen, ovary and liver.

Able to homodimerize. Interacts with DDX6 and EDC4. Interacts with CCR4-NOT deadenylase complex (By similarity). Interacts with RC3H1; the interaction is RNA independent.

The RING-type zinc finger is required for proper localization to stress granules, but not to P-bodies.

The ROQ region is required for CDE RNA-binding (PubMed:25504471, PubMed:25026078). Has 2 separate RNA-binding sites, one for CDE RNA and the other for dsRNA, both sites are important for mRNA decay (PubMed:25026078). ADE RNA-binding involves an extended binding surface on the ROQ region with a number of additional residues compared with the CDE RNA (By similarity). It may also be involved in localization to stress granules (By similarity).

HEPN (higher eukaryotes and prokaryotes nucleotide-binding) are observed in both N- and C-terminal sides of ROQ domain with 3D structure even if they are poredcted on the basis of sequence.