The following text describes a protein:
Function:
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. Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs. In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4/Ox40 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity. In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression. Also recognizes CDE in its own mRNA and in that of paralogous RC3H2, possibly leading to feedback loop regulation. Inhibits cooperatively with ZC3H12A the differentiation of helper T cells Th17 in lungs. They repress target mRNA encoding the Th17 cell-promoting factors IL6, ICOS, REL, IRF4, NFKBID and NFKBIZ. The cooperation requires RNA-binding by RC3H1 and the nuclease activity of ZC3H12A. Recognizes and binds mRNAs containing a hexaloop stem-loop motif, called alternative decay element (ADE). Together with ZC3H12A, destabilizes TNFRSF4/OX40 mRNA by binding to the conserved stem loop structure in its 3'UTR. Able to interact with double-stranded RNA (By similarity). 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 (By similarity).
Miscellaneous:
MISCELLANEOUS: Treatment of C57BL/6 males with ethylnitrosourea led to the identification of the sanroque mouse strain. The causative mutation in sanroque appears to be RC3H1 Arg-199. Homozygous sanroque mice develop high titers of autoantibodies and display excessive numbers of follicular helper T-cells and germinal centers with pattern of pathology consistent with lupus. Sanroque mice reproducibly develop intestinal inflammation in the small intestine but not the colon. Extensive cytokine dysregulation resulting in both over-expression and under-expression of chemotactic cytokines occurs in the ileum, the region most prone to the development of inflammation in sanroque mice. They show up-regulation of expression of at least 15 miRNAs in T cells. The lack of compensation of RC3H1 defects by the RC3H2 paralog in sanroque mice may be due to the fact that the mutated protein may retain its scaffolding position within RNA granules, preventing RC3H2 to access mRNAs to be regulated.
Subcellular Localization:
Cytoplasm, P-body. Cytoplasmic granule. Note=During stress, such as that induced by arsenite treatment, localizes to cytosolic stress granules. Localization to stress granules, but not to P-bodies, depends upon the RING-type zinc finger. ICOS repression may correlate with the localization to P-bodies, not to stress granules.
Domain:
The ROQ region is required for CDE RNA-binding. Has 2 separate RNA-binding sites, one for CDE RNA and the other for dsRNA, both sites are important for mRNA decay (By similarity). ADE RNA-binding involves an extended binding surface on the ROQ region with a number of additional residues compared with the CDE RNA. It may also be involved in localization to stress granules; The RING-type zinc finger may be required for proper localization to stress granules, but not to P-bodies; 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.
Sequence:
MPVQAPQWTDFLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQTTINTDIELLPVNSALLQLVGAQIPEQQPITLCSGVEDTKHYEEAKKCVEELALYLKPLSSARGVGLNSTTQSVLSRPMQRKLVTLVHCQLVEEEGRIRAMRAARSLGERTVTELILQHQNPQQLSSNLWAAVRARGCQFLGPAMQEEALKLVLLALEDGSALSRKVLVLFVVQRLEPRFPQASKTSIGHVVQLLYRASCFKVTKRDEDSSLMQLKEEFRTYEALRREHDSQIVQIAMEAGLRIAPDQWSSLLYGDQSHKSHMQSIIDKLQTPASFAQSVQELTIALQRTGDPANLNRLRPHLELLANIDPSPDAPPPTWEQLENGLVAVRTVVHGLVDYIQNHSKKGADQQQPPQHSKYKTYMCRDMKQRGGCPRGASCTFAHSQEELEKFRKMNKRLVPRRPLSASLGQLNEVGLPSAPILSDESAVDLSNRKPPALPNGIASSGSTVTQLIPRGTDPSFDSSLKPVKLDHLSSSAPGSPPDLLESAPKSISALPVNPHPVPPRGPTDLPPMPVTKPIQMVPRGSQLYPAQQADVYYQDPRGSAPAFETAPYQQGMYYTPPPCVSRFVRPPPSAPEPGPPYLDHYSPYLQDRVINSQYGTQPQQYPPMYPAHYDGRRVYPAQSYTREEMFRESPIPIDIPSAAVPSYVPESRERYQQVEGYYPVAPHPAQIRPSYPRDPPYSRLPPPQPHPSLDELHRRRKEIMAQLEERKVISPPPFAPSPTLPPAFHPEEFLDEDLKVAGKYKANDYSQYSPWSCDTIGSYIGTKDAKPKDVVAAGSVEMMNVESKGTREQRLDLQRRAVETSDDDLIPFGDRPTVSRFGAISRTSKTLYQGAGPLQAIAPQGAPTKSINISDYSAYGAHGGWGDSPYSPHANIPPQGHFIEREKMSMAEVASHGKPLLSAEREQLRLELQQLNHQISQQTQLRGLEAVSNRLVLQREVNTLASQPQPPQLPPKWPGMISSEQLSLELHQVEREIGKRTRELSMENQCSVDMKSKLGTSKQAENGQPEPQNKIRTEDLTLTFSDVPNGSALTQENLSLLSNKTSSLNLSEDSEGGGDNNDSQRSGVVSNSAP