摘要
Abstract The dopamine transporter （DAT） is involved in the regulation of extracellular dopamine levels. A 40-bp variable-number tandem repeat （VNTR） polymorphism in the 3-untranslated region （3UTR） of the DAT has been reported to be associated with various phenotypes that are involved in the aberrant regulation of dopaminergic neu- rotransmission. In the present study, we found that miR- 137 and miR-491 caused a marked reduction of DAT expression, thereby influencing neuronal dopamine trans- port. Moreover, the regulation of miR-137 and miR-491 on this transport disappeared after the DAT was silenced. The miR-491 seed region that is located on the VNTR sequence in the 3＇UTR of the DAT and the regulatory effect of miR- 491 on the DAT depended on the VNTR copy-number. These data indicate that miR-137 and miR-491 regulate DAT expression and dopamine transport at the post- transcriptional level, suggesting that microRNA may be targeted for the treatment of diseases associated with DAT dysfunction.
The dopamine transporter （DAT） is involved in the regulation of extracellular dopamine levels. A 40-bp variable-number tandem repeat （VNTR） polymorphism in the 3-untranslated region （3UTR） of the DAT has been reported to be associated with various phenotypes that are involved in the aberrant regulation of dopaminergic neu- rotransmission. In the present study, we found that miR- 137 and miR-491 caused a marked reduction of DAT expression, thereby influencing neuronal dopamine trans- port. Moreover, the regulation of miR-137 and miR-491 on this transport disappeared after the DAT was silenced. The miR-491 seed region that is located on the VNTR sequence in the 3＇UTR of the DAT and the regulatory effect of miR- 491 on the DAT depended on the VNTR copy-number. These data indicate that miR-137 and miR-491 regulate DAT expression and dopamine transport at the post- transcriptional level, suggesting that microRNA may be targeted for the treatment of diseases associated with DAT dysfunction.
作者
Xiaojian Jia
Feng Wang
Ying Han
XuewenGeng
Minghua Li
Yu Shi
Lin Lu
Yun Chen
Xiaojian Jia;Feng Wang;Ying Han;XuewenGeng;Minghua Li;Yu Shi;Lin Lu;Yun Chen(Shenzhen Key Laboratory for Drug Addiction and Medication Safety,Department of Ultrasound,Peking University Shenzhen Hospital,Biomedical Research Institute,Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center,Shenzhen 518036,China;Institute of Mental Health,Peking University Sixth Hospitaland Key Laboratory of Mental Health,National Institute on Drug Dependence,Peking University,Beijing 100191,China;Department of Physiology and Neurobiology,Xinxiang Medical University,Xinxiang 453000,China)
基金
supported by grants from the National Postdoctoral Science Foundation,China(2014M552219)
the Natural Science Foundation of Guangdong Province,China(2015 A030313889,2015A030401013,2014A030313709,and 2014A030 313710)
the Science and Technology Planning Project of Shenzhen Municipality,China(ZDSYS201504301045406,JCYJ20150403110 829621,JCYJ20150403091443301,JCYJ20140415162542975,JCYJ 20140415162338855,JCYJ20140828163634004,and JCYJ201206 16144352139)
the Health and Family Planning Commission Project of Shenzhen Municipality,China(201401026)
