Titel
Tristetraprolin binding site atlas in the macrophage transcriptome reveals a switch for inflammation resolution
Autor*in
Vitaly Sedlyarov
Max F. Perutz Laboratories, Univeristät Wien
Autor*in
Florian Ebner
Max F. Perutz Laboratories, Univeristät Wien
... show all
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. By functionally relating TTP binding sites to mRNA stability and levels, we identify a TTP‐controlled switch for the transition from inflammatory into the resolution phase of the macrophage immune response. Mapping of binding positions of the mRNA‐stabilizing protein HuR reveals little target and functional overlap with TTP, implying a limited co‐regulation of inflammatory mRNA decay by these proteins. Our study establishes a functionally annotated and navigable transcriptome‐wide atlas (http://ttp-atlas.univie.ac.at) of cis‐acting elements controlling mRNA decay in inflammation.
Stichwort
mRNA decayinflammationmacrophagePAR‐CLIP
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
https://phaidra.univie.ac.at/o:533926
Erschienen in
Titel
Molecular Systems Biology
Band
12
Ausgabe
5
Verlag
EMBO
Erscheinungsdatum
2016
Zugänglichkeit

Herunterladen

Universität Wien | Universitätsring 1 | 1010 Wien | T +43-1-4277-0