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RC3H1 is a multifunctional regulator of immune homeostasis. (Review)
Crystal structures, small-angle X-ray scattering, and E2 profiling revealed that while the two paralogs are highly homologous, RC3H2 and RC3H1 are different in their structures and functions.
A distinct, sequence-induced conformation is required for recognition of the constitutive decay element RNA by Roquin.
Roquin-1 and roquin-2 proteins function redundantly in mRNA degradation.
RC3H1 binds preferentially short-lived and DNA damage-induced mRNAs. Knockdown of RC3H1 resulted in increased A20 (Montrer TNFAIP3 Kits ELISA) protein expression, thereby interfering with IkappaB kinase (Montrer CHUK Kits ELISA) and NF-kappaB (Montrer NFKB1 Kits ELISA) activities.
In this review we summarize current progress regarding the specific characteristics of sequences and structures in the 3' untranslated regions of mRNAs that are recognized by tristetraproline (Montrer ZFP36 Kits ELISA), Roquins, and Regnase-1.
Roquin binding to target mRNAs involves a winged helix-turn-helix motif.
Findings reveal that differential regulation of mRNAs by Regnase-1 and Roquin depends on their translation status and enables elaborate control of inflammation.
Roquin-mediated degradation of HMGXB3 and IL6 (Montrer IL6 Kits ELISA) mRNAs in human cells, demonstrates the importance of both binding sites for mRNA decay.
Excessive interferon (IFN)-gamma (Montrer IFNA Kits ELISA) signaling promotes accumulation of Roquin-mutated, short-lived effector-like CD8 (Montrer CD8A Kits ELISA)+ T cells in autoimmune-prone transgenic mice.
mutations of both Regnase-1 and Roquin in T cells leads to massive lymphocyte activation and increased TH1 (Montrer HAND1 Kits ELISA) cells. In contrast, mutation of either Regnase-1 or Roquin affected T cell activation to a lesser extent than the double mutation, indicating that Regnase-1 and Roquin function nonredundantly in T cells. Regnase-1 is capable of repressing Roquin mRNA.
Roquin-mediated control of PI3K-mTOR (Montrer FRAP1 Kits ELISA) signaling prevents autoimmunity by restraining activation and differentiation of conventional T cells and specialization of Treg cells.
these studies suggest that modulation of Roquin in myeloid cells may reduce both inflammation and bacterial growth during the chronic phase of Mycobacterium tuberculosis infection
The authors unexpectedly uncover a ROQUIN-AMPK (Montrer PRKAA1 Kits ELISA) metabolic signaling nexus essential for selectively promoting T follicular helper cell responses.
Crystal structures and NMR data show that the Roquin-1 ROQ domain recognizes hexaloops in the SELEX-derived alternative decay element (ADE) and in an ADE-like variant present in the Ox40 (Montrer TNFRSF4 Kits ELISA) 3'-UTR (Montrer UTS2R Kits ELISA) with identical binding modes.
Roquin also directly binds Argonaute2 (Montrer EIF2C2 Kits ELISA), a central component of the RNA-induced silencing complex, and miR (Montrer MLXIP Kits ELISA)-146a, a microRNA that targets Icos (Montrer ICOS Kits ELISA) mRNA.
small intestinal inflammation in Rc3h1(san/san) and Rc3h1(gt/gt (Montrer FABP6 Kits ELISA)) mice is due to a failure of Roquin expression in the immune system and not to insufficient systemic Roquin expression.
Over-expression of Roquin exacerbates T-cell mediated hepatitis.
Roquin inhibited T(H)17 cell differentiation and acted together with the endoribonuclease regnase-1 to repress target mRNA encoding the T(H)17 cell-promoting factors IL-6 (Montrer IL6 Kits ELISA), ICOS (Montrer ICOS Kits ELISA), c-Rel (Montrer NFkBP65 Kits ELISA), IRF4 (Montrer IRF4 Kits ELISA), IkappaBNS and IkappaBzeta (Montrer NFKBIZ Kits ELISA).
RC3H1, or roquin, encodes a highly conserved member of the RING type ubiquitin ligase protein family (Vinuesa et al., 2005
RING finger and C3H zinc finger protein 1
, RING finger protein 198
, probable E3 ubiquitin-protein ligase Roquin
, ring finger and CCCH-type zinc finger domains 1
, ring finger and CCCH-type domains 1
, protein Sanroque
, RING CCCH (C3H) domains 1
, RING finger and CCCH-type zinc finger domain-containing protein 1