Abstract 1312: Functional significance for an hnRNP A18 signature RNA motif in the 3'UTR of Ataxia Telangiectasia and RAD3 related (ATR) transcript

Abstract

Abstract The predominantly nuclear hnRNP A18 translocates to the cytosol in response to cellular stress and increases translation by specifically binding to the 3'untranslated region (UTR) of several mRNA transcripts and the eukaryotic Initiation Factor 4G. Here, we identified a 51 nucleotides motif that is present 11.49 times more often in the 3'UTR of hnRNP A18 mRNA targets than in the unigene data base. This motif was identified by computational analysis of primary sequences and secondary structures of hnRNP A18 mRNA targets against the unaligned sequences. Band shift analyses indicate that the motif is sufficient to confer binding to hnRNP A18. A search of the entire unigene data base indicates that the hnRNP A18 motif is also present in the 3'UTR of the Ataxia Telangiectasia and Rad3 related (ATR) mRNA. Validation of the predicted hnRNP A18 motif is provided by hnRNP A18 binding to ATR 3'UTR and amplification of endogenous ATR transcript on polysomal fractions immunoprecipitated with hnRNP A18 antibodies. Moreover, over expression of hnRNP A18 results in increased ATR protein levels and increased phosphorylation of Chk1, a preferred ATR substrate, in response to UV radiation. To our knowledge, this constitutes the first demonstration of a post-transcriptional regulatory mechanism for ATR activity. hnRNP A18 could thus become a new target to trigger ATR activity as back up stress-response mechanisms to functionally compensate for absent or defective genotoxic stress responders. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1312.