Tristetraprolin binding site atlas in the macrophage transcriptome reveals a switch for inflammation resolution.

ABSTRACT: Precise regulation of mRNA decay is fundamental for robust yet not exaggerated inflammatory responses to pathogens. However, a global model integrating regulation and functional consequences of inflammation-associated mRNA decay remains to be established. Using time-resolved high-resolution RNA binding analysis of the mRNA-destabilizing protein tristetraprolin (TTP), an inflammation-limiting factor, we qualitatively and quantitatively characterize TTP binding positions in the transcriptome of immunostimulated macrophages. We identify pervasive destabilizing and non-destabilizing TTP binding, including a robust intronic binding, showing that TTP binding is not sufficient for mRNA destabilization. A low degree of flanking RNA structuredness distinguishes occupied from silent binding motifs.

SUBMITTER: Sedlyarov V 

PROVIDER: S-EPMC4988506 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature