MicroRNA-mediated up-regulation of an alternatively polyadenylated variant of the mouse cytoplasmic beta-actin gene Export

@article{ghosh08, abstract = {Actin is a major cytoskeletal protein in eukaryotes. Recent studies suggest more diverse functional roles for this protein. Actin mRNA is known to be localized to neuronal synapses and undergoes rapid deadenylation during early developmental stages. However, its 3'-untranslated region (UTR) is not characterized and there are no experimentally determined polyadenylation (polyA) sites in actin mRNA. We have found that the cytoplasmic {beta}-actin (Actb) gene generates two alternative transcripts terminated at tandem polyA sites. We used 3'-RACE, EST end analysis and in situ hybridization to unambiguously establish the existence of two 3'-UTRs of varying length in Actb transcript in mouse neuronal cells. Further analyses showed that these two tandem polyA sites are used in a tissue-specific manner. Although the longer 3'-UTR was expressed at a relatively lower level, it conferred higher translational efficiency to the transcript. The longer transcript harbours a conserved mmu-miR-34a/34b-5p target site. Sequence-specific anti-miRNA molecule, mutations of the miRNA target region in the 3'-UTR resulted in reduced expression. The expression was restored by a mutant miRNA complementary to the mutated target region implying that miR-34 binding to Actb 3'-UTR up-regulates target gene expression. Heterogeneity of the Actb 3'-UTR could shed light on the mechanism of miRNA-mediated regulation of messages in neuronal cells. 10.1093/nar/gkn624}, author = {Ghosh, Tanay and Soni, Kartik and Scaria, Vinod and Halimani, Mahantappa and Bhattacharjee, Chaitali and Pillai, Beena}, citeulike-article-id = {3474028}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/nar/gkn624}, citeulike-linkout-1 = {http://nar.oxfordjournals.org/cgi/content/abstract/36/19/6318}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18835850}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18835850}, day = {3}, doi = {10.1093/nar/gkn624}, journal = {Nucl. Acids Res.}, keywords = {microrna, microrna\_activation, polya}, month = {October}, pages = {gkn624+}, posted-at = {2009-03-24 16:21:43}, priority = {2}, title = {MicroRNA-mediated up-regulation of an alternatively polyadenylated variant of the mouse cytoplasmic {beta}-actin gene}, url = {http://dx.doi.org/10.1093/nar/gkn624}, year = {2008} }

TY - JOUR ID - ghosh08 L3 - citeulike-article-id:3474028 N2 - Actin is a major cytoskeletal protein in eukaryotes. Recent studies suggest more diverse functional roles for this protein. Actin mRNA is known to be localized to neuronal synapses and undergoes rapid deadenylation during early developmental stages. However, its 3'-untranslated region (UTR) is not characterized and there are no experimentally determined polyadenylation (polyA) sites in actin mRNA. We have found that the cytoplasmic {beta}-actin (Actb) gene generates two alternative transcripts terminated at tandem polyA sites. We used 3'-RACE, EST end analysis and in situ hybridization to unambiguously establish the existence of two 3'-UTRs of varying length in Actb transcript in mouse neuronal cells. Further analyses showed that these two tandem polyA sites are used in a tissue-specific manner. Although the longer 3'-UTR was expressed at a relatively lower level, it conferred higher translational efficiency to the transcript. The longer transcript harbours a conserved mmu-miR-34a/34b-5p target site. Sequence-specific anti-miRNA molecule, mutations of the miRNA target region in the 3'-UTR resulted in reduced expression. The expression was restored by a mutant miRNA complementary to the mutated target region implying that miR-34 binding to Actb 3'-UTR up-regulates target gene expression. Heterogeneity of the Actb 3'-UTR could shed light on the mechanism of miRNA-mediated regulation of messages in neuronal cells. 10.1093/nar/gkn624 JF - Nucl. Acids Res. TI - MicroRNA-mediated up-regulation of an alternatively polyadenylated variant of the mouse cytoplasmic {beta}-actin gene SP - gkn624 KW - microrna KW - microrna_activation KW - polya AU - Ghosh, Tanay AU - Soni, Kartik AU - Scaria, Vinod AU - Halimani, Mahantappa AU - Bhattacharjee, Chaitali AU - Pillai, Beena PY - 2008/10/03/ UR - http://dx.doi.org/10.1093/nar/gkn624 ER -