Toll IL-1 receptors differ in their ability to promote the stabilization of adenosine and uridine-rich elements containing mRNA.
Several ligands for Toll IL-1R (TIR) family are known to promote stabilization of a subset of short-lived mRNAs containing AU-rich elements (AREs) in their 3' untranslated regions. It is now evident however, that members of the TIR family may use distinct intracellular signaling pathways to achieve a spectrum of biological end points. Using human embryonic kidney 293 cells transfected to express different TIRs we now report that signals initiated through IL-1R1 or TLR4 but not TLR3 can promote the stabilization of unstable chemokine mRNAs. Similar results were obtained when signaling from endogenous receptors was examined using a mouse endothelial cell line (H5V). The ability of TIR family members to stabilize ARE-containing mRNAs results from their differential use of signaling adaptors MyD88, MyD88 adaptor-like protein, Toll receptor IFN-inducing factor (Trif), and Trif-related adaptor molecule. Overexpression of MyD88 or MyD88 adaptor-like protein was able to promote enhanced stability of ARE-containing mRNA, whereas Trif and Trif-related adaptor molecule exhibited markedly reduced capacity. Hence the ability of TIRs to signal stabilization of mRNA appears to be linked to the MyD88-dependent signaling pathway.
Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Shyamasree
S
Datta
Michael
M
Novotny
Xiaoxia
X
Li
Julie
J
Tebo
Thomas A
TA
Hamilton
D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000276:immunology / Q000378:metabolism*; D053573:Receptors, Interleukin-1 Type I; D015398:Signal Transduction / Q000502:physiology; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014162:Transfection; D014529:Uridine / Q000378:metabolism*
D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000943:Antigens, Differentiation; D018925:Chemokines; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; C434984:TIRAP protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000241:Adenosine; D014529:Uridine