(9)-(14) Post-transcriptional regulation determines the fate of mRNA in association with RNA-binding proteins (RBPs), including tristetraprolin (TTP), ARE/poly-(U) binding degradation factor 1 (AUF1), Regnase-1 (also known as Zc3h12a and Mcpip1), Roquin and AT-rich interactive domain-containing 5a (Arid5a).
In addition to AREs, stem-loop structures with a pyrimidinepurine -pyrimidine (Py-Pu-Py) tri-loop sequence in 3' UTR of inflammatory mRNAs are also recognized by a set of RBPs, including Regnase-1, Roquin and Arid5a, for controlling degradation of mRNA.
Critical roles of Arid5a in stabilizing stem-loop mRNA for enhancing inflammation
Stem-loop structures with a Py-Pu-Py loop in 3' UTR are also recognized by another RBP, Arid5a. (66) In contrast to Regnase-1 and Roquin, Arid5a stabilizes target mRNAs by inhibiting the actions of Regnase-1 and Roquin.
Abbreviations: Regnase-1: Regulatory RNase 1; ARE: adenine- and uridine-rich element; AUF1: ARE/poly-(U) binding degradation factor 1; Dendritic cells: DCs; TLRs: Toll-like receptors; TNF: tumor necrosis factor; interleukin-6: IL6; TTP: tristetraprolin; PAMPs: pathogen-associated molecular patterns; PRRs: pattern-recognition receptors; RBPs: RNA-binding proteins; RLRs: Retinoic acid-Inducible Gene-I-like receptors; IFN: Interferon; IRFs: IFN-regulatory factors; C/EBPO: CCAAT/ enhancer-binding protein [beta]; TIA-1: T-cell-restricted intracellular antigen-1; TIAR: TIA-1-related protein; Tfh cells: Follicular helper T cells; PBs: Processing bodies; SGs: Stress granules; LPS: Lipopolysaccharide; Py-Pu-Py: pyrimidine-purine-pyrimidine; Arid5a: AT-rich interactive domain-containing 5a.
(2013) Arid5a controls IL-6 mRNA stability, which contributes to elevation of IL-6 level in vivo.
(2016) Arid5a regulates naive [CD4.sup.+] T cell fate through selective stabilization of Stat3 mRNA.
(2016) Arid5a exacerbates IFN-gamma-mediated septic shock by stabilizing T-bet mRNA.
(2017) TLR4-induced NF-kappaB and MAPK signaling regulate the IL-6 mRNA stabilizing protein Arid5a. Nucleic Acids Res.