MicroRNAs regulate synthesis of the neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells

@article{citeulike:2465103, abstract = {MicroRNAs (miRNAs) are a class of 19- to 23-nt, small, noncoding RNAs, which bind the 3' UTR of target mRNAs to mediate translational repression in animals. miRNAs have been shown to regulate developmental processes, such as self-renewal of stem cells, neuronal differentiation, myogenesis, and cancer. A functional role of miRNAs in the regulation of neurotransmitter synthesis has yet to be ascribed. We used mesenchymal stem cells (MSCs) as a model to study miRNA-mediated neurotransmitter regulation in developing neuronal cells. MSCs are mesoderm-derived cells, primarily resident in adult bone marrow, which can generate functional neuronal cells. We have previously shown that human MSC-derived neuronal cells express the neurotransmitter gene, Tac1, but do not synthesize the gene's encoded peptide, the neurotransmitter substance P (SP), unless stimulated with the inflammatory mediator IL-1{alpha}. These findings suggested a potential role for miRNAs in the regulation of SP synthesis. Here, we report on the miRNA profile of undifferentiated human MSCs and MSC-derived neuronal cells by using miRNA-specific bioarrays. miRNAs that were increased in the neuronal cells and decreased after IL-1{alpha} stimulation were analyzed by the miRanda algorithm to predict Tac1 mRNA targets. Putative miR-130a, miR-206, and miR-302a binding sites were predicted within the 3' UTR of Tac1. Target validation using a luciferase reporter system confirmed the miR-130a and miR-206 sites. Specific inhibition of miR-130a and miR-206 in the neuronal cells resulted in SP synthesis and release. The studies provide a different approach in ascribing a new regulatory role for miRNAs in regulating neurotransmitter synthesis. 10.1073/pnas.0703037104}, author = {Greco, Steven J. and Rameshwar, Pranela }, citeulike-article-id = {2465103}, doi = {http://dx.doi.org/10.1073/pnas.0703037104}, journal = {Proceedings of the National Academy of Sciences}, keywords = {microrna, microrna\_expression, msc}, month = {September}, number = {39}, pages = {15484--15489}, posted-at = {2008-03-04 15:16:44}, priority = {2}, title = {MicroRNAs regulate synthesis of the neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells}, url = {http://dx.doi.org/10.1073/pnas.0703037104}, volume = {104}, year = {2007} }

TY - JOUR ID - citeulike:2465103 L3 - citeulike-article-id:2465103 TI - MicroRNAs regulate synthesis of the neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells JF - Proceedings of the National Academy of Sciences VL - 104 IS - 39 SP - 15484 EP - 15489 N2 - MicroRNAs (miRNAs) are a class of 19- to 23-nt, small, noncoding RNAs, which bind the 3' UTR of target mRNAs to mediate translational repression in animals. miRNAs have been shown to regulate developmental processes, such as self-renewal of stem cells, neuronal differentiation, myogenesis, and cancer. A functional role of miRNAs in the regulation of neurotransmitter synthesis has yet to be ascribed. We used mesenchymal stem cells (MSCs) as a model to study miRNA-mediated neurotransmitter regulation in developing neuronal cells. MSCs are mesoderm-derived cells, primarily resident in adult bone marrow, which can generate functional neuronal cells. We have previously shown that human MSC-derived neuronal cells express the neurotransmitter gene, Tac1, but do not synthesize the gene's encoded peptide, the neurotransmitter substance P (SP), unless stimulated with the inflammatory mediator IL-1{alpha}. These findings suggested a potential role for miRNAs in the regulation of SP synthesis. Here, we report on the miRNA profile of undifferentiated human MSCs and MSC-derived neuronal cells by using miRNA-specific bioarrays. miRNAs that were increased in the neuronal cells and decreased after IL-1{alpha} stimulation were analyzed by the miRanda algorithm to predict Tac1 mRNA targets. Putative miR-130a, miR-206, and miR-302a binding sites were predicted within the 3' UTR of Tac1. Target validation using a luciferase reporter system confirmed the miR-130a and miR-206 sites. Specific inhibition of miR-130a and miR-206 in the neuronal cells resulted in SP synthesis and release. The studies provide a different approach in ascribing a new regulatory role for miRNAs in regulating neurotransmitter synthesis. 10.1073/pnas.0703037104 KW - microrna KW - microrna_expression KW - msc AU - Greco, Steven AU - Rameshwar, Pranela PY - 2007/09/25/ UR - http://dx.doi.org/10.1073/pnas.0703037104 ER -