YB-1 Binds to GluR2 mRNA and CaM1 mRNA in the Brain and Regulates their Translational Levels in an Activity-Dependent Manner |
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Authors: | Toru Tanaka Sachiyo Ohashi Tomoko Funakoshi Shunsuke Kobayashi |
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Institution: | (1) Research Unit of Biochemistry, School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi Chiba, 274-8555, Japan;(2) Present address: Cellular Dynamics Laboratory, RIKEN Advanced Science Institute, Hirosawa, Wako Saitama, 351-0198, Japan; |
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Abstract: | The translational regulator YB-1 binds to mRNAs. In the brain, YB-1 is prominently expressed from the prenatal stage until
the first week after birth, being associated with polysomes and distributed in neuronal dendrites, but its expression declines
to a much lower level thereafter. It is therefore of interest to identify the mRNAs whose translation is controlled by YB-1
in the postnatal growing brain. In this study we found that YB-1 interacted with the mRNAs for glutamate receptor subunit
2 (GluR2) and calmodulin1 (CaM1) in both brain and NG108-15 cells. Overexpression or knockdown of YB-1 altered the levels
of these proteins significantly in cultured cells without any change in their mRNA levels. When the cells were treated with
neurotransmitters, translation of these proteins was induced within a short time, and a change in the amount of YB-1 on its
target mRNAs was observed in the heavy-sedimenting polysome fractions on a sucrose gradient. Depletion of YB-1 expression
by siRNA abrogated the translational activation. Furthermore, in the brain of kainic acid-treated mice, the distribution of
YB-1 was shifted to much heavier fractions associated with polysomes within 30 min to 1 h after the treatment, and the distribution
returned to lighter fractions within the following 2 h. The protein levels of GluR2 and CaM1 were also increased transiently
when the distribution of YB-1 on the gradient changed. These results suggest that in the brain of growing mice, YB-1 binds
to GluR2 and CaM1 mRNAs and regulates their translation in an activity-dependent manner. |
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