Protein: Roquin-1 (Roquin) (EC 2.3.2.27) (Protein Sanroque) (RING finger and C3H zinc finger protein 1) (RING finger and CCCH-type zinc finger domain-containing protein 1) (Q4VGL6)
Organism: Mus musculus (Mouse)
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).
Subcellular location: Cytoplasm, P-body {ECO:0000269|PubMed:15917799, ECO:0000269|PubMed:20412057, ECO:0000269|PubMed:20639877, ECO:0000269|PubMed:23583642, ECO:0000269|PubMed:26000482}. Cytoplasmic granule {ECO:0000269|PubMed:26000482}. Note=During stress, such as that induced by arsenite treatment, localizes to cytosolic stress granules (PubMed:26000482). 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 (PubMed:20639877). {ECO:0000269|PubMed:20639877, ECO:0000269|PubMed:26000482}.
Interaction partners:
- Endoribonuclease ZC3H12A
- Inducible T-cell costimulator
- CCR4-NOT transcription complex subunit 1
- FMR1-interacting protein NUFIP2
- Protein argonaute-2
- Roquin-2
Sequence:
MPVQAPQWTDFLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQTTINTDIELLPVNSALLQLVGAQIPEQQPITLCSGVEDTKHYEEAKKCVEELALYLKPLSSARGVGLNSTTQSVLSRPMQRKLVTLVHCQLVEEEGRIRAMRAARSLGERTVTELILQHQNPQQLSSNLWAAVRARGCQFLGPAMQEEALKLVLLALEDGSALSRKVLVLFVVQRLEPRFPQASKTSIGHVVQLLYRASCFKVTKRDEDSSLMQLKEEFRTYEALRREHDSQIVQIAMEAGLRIAPDQWSSLLYGDQSHKSHMQSIIDKLQTPASFAQSVQELTIALQRTGDPANLNRLRPHLELLANIDPSPDAPPPTWEQLENGLVAVRTVVHGLVDYIQNHSKKGADQQQPPQHSKYKTYMCRDMKQRGGCPRGASCTFAHSQEELEKFRKMNKRLVPRRPLSASLGQLNEVGLPSAPILSDESAVDLSNRKPPALPNGIASSGSTVTQLIPRGTDPSFDSSLKPVKLDHLSSSAPGSPPDLLESAPKSISALPVNPHPVPPRGPTDLPPMPVTKPIQMVPRGSQLYPAQQADVYYQDPRGSAPAFETAPYQQGMYYTPPPCVSRFVRPPPSAPEPGPPYLDHYSPYLQDRVINSQYGTQPQQYPPMYPAHYDGRRVYPAQSYTREEMFRESPIPIDIPSAAVPSYVPESRERYQQVEGYYPVAPHPAQIRPSYPRDPPYSRLPPPQPHPSLDELHRRRKEIMAQLEERKVISPPPFAPSPTLPPAFHPEEFLDEDLKVAGKYKANDYSQYSPWSCDTIGSYIGTKDAKPKDVVAAGSVEMMNVESKGTREQRLDLQRRAVETSDDDLIPFGDRPTVSRFGAISRTSKTLYQGAGPLQAIAPQGAPTKSINISDYSAYGAHGGWGDSPYSPHANIPPQGHFIEREKMSMAEVASHGKPLLSAEREQLRLELQQLNHQISQQTQLRGLEAVSNRLVLQREVNTLASQPQPPQLPPKWPGMISSEQLSLELHQVEREIGKRTRELSMENQCSVDMKSKLGTSKQAENGQPEPQNKIRTEDLTLTFSDVPNGSALTQENLSLLSNKTSSLNLSEDSEGGGDNNDSQRSGVVSNSAP