title: miR-29a regulates the proliferation and differentiation of retinal progenitors by targeting Rbm8a.
abstract: During development, tight regulation of the expansion of retinal progenitor cells (RPCs) and their differentiation into neuronal and glial cells is important for retinal formation and function. Our study demonstrated that microRNA (miR)-29a modulated the proliferation and differentiation of RPCs by suppressing RBM8A (one of the factors in the exon junction complex). Particularly, overexpression of miR-29a reduced RPC proliferation but accelerated RPC differentiation. By contrast, reduction of endogenous miR-29a elicited the opposite effects. Overexpression of miR-29a repressed the translation of Rbm8a, thus negatively regulating RPC proliferation and promoting the neuronal and glial differentiation of RPCs, and knockdown of endogenous Rbm8a phenocopied the observed effects of miR-29a overexpression. Furthermore, a luciferase reporter assay showed that miR-29a directly interacted with the Rbm8a mRNA 3'UTR, which indicated that Rbm8a is the direct target of miR-29a. To further verify the result, co-overexpression of the Rbm8a 3' UTR-wt (plasmids into which the Rbm8a 3' UTR sequence had been introduced) and miR-29a in RPCs rescued the phenotype associated with miR-29a overexpression, reversing the promotion of differentiation and inhibition of proliferation. These results show a novel mechanism by which miR-29a regulates the proliferation and differentiation of RPCs through Rbm8a.
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Bingqiao
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Yuyao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Ni
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics*; D012160:Retina / Q000166:cytology* / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; C586565:RBM8A protein, mouse; D016601:RNA-Binding Proteins
keywords: RBM8A; differentiation; microRNA (miR)-29a; proliferation; retinal progenitor cells