Abstract
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 α1). 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4197-4210 |
| Number of pages | 14 |
| Journal | Molecular and Cellular Biology |
| Volume | 30 |
| Issue number | 17 |
| DOIs | |
| State | Published - Sep 2010 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
miR-375 inhibits differentiation of neurites by lowering HuD levels. / Abdelmohsen, Kotb; Hutchison, Emmette R.; Lee, Eun Kyung; Kuwano, Yuki; Kim, Mihee M.; Masuda, Kiyoshi; Srikantan, Subramanya; Subaran, Sarah S.; Marasa, Bernard S.; Mattson, Mark P.; Gorospe, Myriam.
In: Molecular and Cellular Biology, Vol. 30, No. 17, 09.2010, p. 4197-4210.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - miR-375 inhibits differentiation of neurites by lowering HuD levels
AU - Abdelmohsen, Kotb
AU - Hutchison, Emmette R.
AU - Lee, Eun Kyung
AU - Kuwano, Yuki
AU - Kim, Mihee M.
AU - Masuda, Kiyoshi
AU - Srikantan, Subramanya
AU - Subaran, Sarah S.
AU - Marasa, Bernard S.
AU - Mattson, Mark P.
AU - Gorospe, Myriam
PY - 2010/9
Y1 - 2010/9
N2 - 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 α1). 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.
AB - 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 α1). 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.
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U2 - 10.1128/MCB.00316-10
DO - 10.1128/MCB.00316-10
M3 - Article
VL - 30
SP - 4197
EP - 4210
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 17
ER -