한빛사논문
Youngseob Jung1,*, Ji-Young Seo1, Hye Guk Ryu2, Do-Yeon Kim3, Kyung-Ha Lee4 and Kyong-Tai Kim1,†
1Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, Republic of Korea.
2Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, Republic of Korea.
3Department of Pharmacology, School of Dentistry, Brain Science and Engineering Institute, Kyungpook National University, Daegu 41940, Republic of Korea.
4Division of Cosmetic Science and Technology, Daegu Haany University, Gyeongbuk 38610, Republic of Korea.
†Corresponding author.
*Present address: Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Abstract
The AMPA receptor subunit GluA1 is essential for induction of synaptic plasticity. While various regulatory mechanisms of AMPA receptor expression have been identified, the underlying mechanisms of GluA1 protein synthesis are not fully understood. In neurons, axonal and dendritic mRNAs have been reported to be translated in a cap-independent manner. However, molecular mechanisms of cap-independent translation of synaptic mRNAs remain largely unknown. Here, we show that GluA1 mRNA contains an internal ribosome entry site (IRES) in the 5′UTR. We also demonstrate that heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 interacts with GluA1 mRNA and mediates internal initiation of GluA1. Brain-derived neurotrophic factor (BDNF) stimulation increases IRES-mediated GluA1 translation via up-regulation of HNRNP A2/B1. Moreover, BDNF-induced GluA1 expression and dendritic spine density were significantly decreased in neurons lacking hnRNP A2/B1. Together, our data demonstrate that IRES-mediated translation of GluA1 mRNA is a previously unidentified feature of local expression of the AMPA receptor.
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