Tristetraprolin Inhibits Poly(A)-Tail Synthesis in Nuclear mRNA that Contains AU-Rich Elements by Interacting with Poly(A)-Binding Protein Nuclear 1

• DOI: 10.1371/journal.pone.0041313
• Publication Date: 2012-07-27T03:22:31Z
• Authors: Yu-Lun Su; Shun-Chang Wang; Pei-Yu Chiang; Nien-Yi Lin; Yu-Fang Shen; Geen-Dong Chang; Ching-Jin Chang
• Keywords: Tristetraprolin

Tristetraprolin binds mRNA AU-rich elements and thereby facilitates the destabilization of mature in cytosol.To understand how tristetraprolin mechanistically functions, we biopanned with a phage-display library for proteins that interact retrieved, among others, fragment poly(A)-binding protein nuclear 1, which assists 3'-polyadenylation by binding to immature poly(A) tails increases activity polymerase, is directly responsible polyadenylation. The tristetraprolin/poly(A)-binding 1 interaction was characterized using deletion mutants pull-down co-immunoprecipitation assays. interacted carboxyl-terminal region via its tandem zinc finger domain another region. Although are located both cytoplasm nucleus, they vivo only nucleus. In vitro, bound polymerase inhibited polyadenylation element-containing mRNAs encoding tumor necrosis factor α, GM-CSF, interleukin-10. A domain-deleted mutant less effective inhibitor. Expression restricted nucleus resulted downregulation an α/luciferase construct.In addition known cytosolic mRNA-degrading function, inhibits tail synthesis interacting regulate expression mRNA.