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Báo cáo y học: " Evidence for natural antisense transcript-mediated inhibition of microRNA function"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Evidence for natural antisense transcript-mediated inhibition of microRNA function. | Faghihi et al. Genome Biology 2010 11 R56 http genomebiology.eom 2010 11 5 R56 w Genome Biology RESEARCH _ Open Access Evidence for natural antisense transcript-mediated inhibition of mieroRNA function Mohammad Ali Faghihi 1 Ming Zhang3 4 Jia Huang5 Farzaneh Modarresi1 Marcel P Van der Brug1 Michael A Nalls6 Mark R Cookson6 Georges St-Laurent III7 and Claes Wahlestedt 1 2 Abstract Background MicroRNAs miRNAs have the potential to regulate diverse sets of mRNA targets. In addition mammalian genomes contain numerous natural antisense transcripts most of which appear to be non-protein-coding RNAs ncRNAs . We have recently identified and characterized a highly conserved non-coding antisense transcript for beta-secretase-1 BACE1 a critical enzyme in Alzheimer s disease pathophysiology. The BACE1 -antisense transcript is markedly up-regulated in brain samples from Alzheimer s disease patients and promotes the stability of the sense BACE1 transcript. Results We report here that BACE1 -antisense prevents miRNA-induced repression of BACE1 mRNA by masking the binding site for miR-485-5p. Indeed miR-485-5p and BACE1 -antisense compete for binding within the same region in the open reading frame of the BACE1 mRNA. We observed opposing effects of BACE1 -antisense and miR-485-5p on BACE1 protein in vitro and showed that Locked Nucleic Acid-antimiR mediated knockdown of miR-485-5p as well as BACE1 -antisense over-expression can prevent the miRNA-induced BACE1 suppression. We found that the expression of BACE1 -antisense as well as miR-485-5p are dysregulated in RNA samples from Alzheimer s disease subjects compared to control individuals. Conclusions Our data demonstrate an interface between two distinct groups of regulatory RNAs in the computation of BACE1 gene expression. Moreover bioinformatics analyses revealed a theoretical basis for many other potential interactions between natural antisense transcripts and miRNAs at the binding sites of the latter. Background Recent .