An ataxia-telangiectasia-mutated (ATM) kinase mediated response to DNA damage down-regulates the mRNA-binding potential of THOC5

• DOI: 10.1261/rna.2820911
• Publication Date: 2011-09-22T05:05:30Z
• Authors: Sheetal Ramachandran; Doan Duy Hai Tran; Sabine Klebba-Fae...; Christian Kardinal; Anthony D. Whetton; Teruko Tamura
• Keywords: 0303 health sciences; Tumor Suppressor Proteins; Down-Regulation; Nuclear Proteins; RNA-Binding Proteins; Cell Cycle Proteins; Ataxia Telangiectasia Mutated Proteins; Protein Serine-Threonine Kinases; DNA-Binding Proteins; Mice; 03 medical and health sciences; Mutation; Animals; RNA, Messenger; Cells, Cultured; DNA Damage

In response to DNA damage, transcription is blocked by inhibition of RNA polymerase II activity. The regulation a preexisting pool mRNAs, therefore, plays key role in repair, cell cycle arrest, or differentiation. THOC5 member the THO complex and export subset mRNA, which an important hematopoiesis maintaining primitive cells. Since three serine residues PEST domain have been shown be directly phosphorylated ataxia-telangiectasia-mutated (ATM) kinase, we examined THOC5-dependent mRNA under damage. We show here that damage drastically decreased cytoplasmic set mRNAs impaired THOC5/mRNA formation. mRNP formed with nonphosphorylation mutant (S307/312/314A) THOC5, but not C-terminal deletion after suggesting its phosphorylation domain, necessary for mRNA-binding potency THOC5. were recovered treatment ATM kinase-specific p53-specific siRNA, as well kinase inhibitor, KU55933, conditions, ATM–kinase–p53 pathway involved this Furthermore, KU55933 damage-induced THOC5mRNP dissociation, indicating activation suppresses ability bind target mRNAs.