miR-375 Inhibits Differentiation of Neurites by Lowering HuD Levels

被引：110

作者：

Abdelmohsen, Kotb ^{[1
]}

Hutchison, Emmette R. ^{[2
,3
]}

Lee, Eun Kyung ^{[1
]}

Kuwano, Yuki ^{[1
]}

Kim, Mihee M. ^{[1
]}

Masuda, Kiyoshi ^{[1
]}

Srikantan, Subramanya ^{[1
]}

Subaran, Sarah S. ^{[4
]}

Marasa, Bernard S. ^{[1
]}

Mattson, Mark P. ^{[2
]}

Gorospe, Myriam ^{[1
]}

机构：

[1] NIA, LCMB, IRP, NIH, Baltimore, MD 21224 USA

[2] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA

[3] Brown Univ, Dept Neurosci, Providence, RI 02912 USA

[4] NIA, Confocal Imaging Facil, Res Resources Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2010年 / 30卷 / 17期

基金：

美国国家卫生研究院;

关键词：

BINDING PROTEIN HUD; GAP-43; MESSENGER-RNA; NEURONAL ELAV PROTEINS; DEPENDENT EXPRESSION; CELL-PROLIFERATION; ANIMAL DEVELOPMENT; UP-REGULATION; PC12; CELLS; MICRORNAS; ASSOCIATION;

D O I：

10.1128/MCB.00316-10

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Neuronal development and plasticity are maintained by tightly regulated gene expression programs. Here, we report that the developmentally regulated microRNA miR-375 affects dendrite formation and maintenance. miR-375 overexpression in mouse hippocampus potently reduced dendrite density. We identified the predominantly neuronal RNA-binding protein HuD as a key effector of miR-375 influence on dendrite maintenance. Heterologous reporter analysis verified that miR-375 repressed HuD expression through a specific, evolutionarily conserved site on the HuD 3' untranslated region. miR-375 overexpression lowered both HuD mRNA stability and translation and recapitulated the effects of HuD silencing, which reduced the levels of target proteins with key functions in neuronal signaling and cytoskeleton organization (N-cadherin, PSD-95, RhoA, NCAM1, and integrin alpha 1). Moreover, the increase in neurite outgrowth after brain-derived neurotrophic factor (BDNF) treatment was diminished by miR-375 overexpression; this effect was rescued by reexpression of miR-375-refractory HuD. Our findings indicate that miR-375 modulates neuronal HuD expression and function, in turn affecting dendrite abundance.

引用

页码：4197 / 4210

页数：14

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