MicroRNAs （miRNAs） are critical for both development and function of the central nervous system. Significant evidence suggests that abnormal expression of miRNAs is associated with neurodevelopmental disorders. MeCP...MicroRNAs （miRNAs） are critical for both development and function of the central nervous system. Significant evidence suggests that abnormal expression of miRNAs is associated with neurodevelopmental disorders. MeCP2 protein is an epigenetic regulator repressing or activating gene transcription by binding to methylated DNA. Both loss-of-function and gain-of-function muta- tions in the MECP2 gene lead to neurodevelopmental disorders such as Rett syndrome, autism and MECP2 duplication syndrome. In this study, we demonstrate that miR-130a inhibits neurite outgrowth and reduces dendritic spine density as well as dendritic complexity. Bioinformatics analyses, cell cultures and biochemical experiments indicate that miR-130a targets MECP2 and down-regulates MeCP2 protein expression. Further- more, expression of the wild-type MeCP2, but not a loss- of-function mutant, rescues the miR-130a-induced phe- notype. Our study uncovers the MECP2 gene as a pre- vious unknown target for miR-130a, supporting that miR-130a may play a role in neurodevelopment by reg- ulating MeCP2. Together with data from other groups,our work suggests that a feedback regulatory mecha- nism involving both miR-130a and MeCP2 may serve to ensure their appropriate expression and function in neural development.展开更多
基金the National Basic Research Program （973 Program） （No. 2013CB917803） and the National Natural Science Foundation of China （Grant No. 91132710）. ZQ is supported by the National Natural Science Foundation of China （Grant Nos. 91432111 and 81527901）. KH is supported by the National Natural Science Foundation of China （Grant Nos. 81070907 and 81271255）. WM is supported by NIH （F30 NS090893）. JYW is supported by NIH （RO1AG033004）.
文摘MicroRNAs （miRNAs） are critical for both development and function of the central nervous system. Significant evidence suggests that abnormal expression of miRNAs is associated with neurodevelopmental disorders. MeCP2 protein is an epigenetic regulator repressing or activating gene transcription by binding to methylated DNA. Both loss-of-function and gain-of-function muta- tions in the MECP2 gene lead to neurodevelopmental disorders such as Rett syndrome, autism and MECP2 duplication syndrome. In this study, we demonstrate that miR-130a inhibits neurite outgrowth and reduces dendritic spine density as well as dendritic complexity. Bioinformatics analyses, cell cultures and biochemical experiments indicate that miR-130a targets MECP2 and down-regulates MeCP2 protein expression. Further- more, expression of the wild-type MeCP2, but not a loss- of-function mutant, rescues the miR-130a-induced phe- notype. Our study uncovers the MECP2 gene as a pre- vious unknown target for miR-130a, supporting that miR-130a may play a role in neurodevelopment by reg- ulating MeCP2. Together with data from other groups,our work suggests that a feedback regulatory mecha- nism involving both miR-130a and MeCP2 may serve to ensure their appropriate expression and function in neural development.
