不均一核糖核蛋白M缺乏通过破坏突触可塑性导致认知缺陷。
hnRNPM deficiency leads to cognitive deficits via disrupting synaptic plasticity.
作者信息
Akinyemi Akinsola Raphael, Li Dingfeng, Zhang Juan, Liu Qiang
机构信息
Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, 230001, China; Neurodegenerative Disease Research Center, University of Science and Technology of China, Hefei, 230026, China; CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, 230026, China.
Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, 230001, China; Neurodegenerative Disease Research Center, University of Science and Technology of China, Hefei, 230026, China; CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, 230026, China; National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, 230029, China.
出版信息
Neurosci Lett. 2021 Apr 23;751:135824. doi: 10.1016/j.neulet.2021.135824. Epub 2021 Mar 13.
RNA metabolism involves complex and regulated processes, some of which include transcription, intracellular transport, translation, and degradation. The involvement of RNA binding proteins in these processes remains mostly uncharacterized regarding brain functions, especially cognition. In this study, we report that knockdown of hnRNPM in the CA1 hippocampal region of the mouse brain leads to learning and memory impairment. This finding is further supported, by the reduction of pre- and post-synaptic protein levels synaptophysin and PSD95. Notably, loss of hnRNPM affects the physiological spine in vivo by impairing the morphology of the dendritic spines. Additionally, our study demonstrates that hnRNPM directly binds to the 3'UTR of synaptophysin and PSD95 mRNAs, resulting in the stabilization of these mRNAs. Together, these findings present novel insight into the regulatory role of hnRNPM in neuronal structure and function.
RNA代谢涉及复杂且受调控的过程，其中一些过程包括转录、细胞内运输、翻译和降解。就大脑功能，尤其是认知而言，RNA结合蛋白在这些过程中的作用大多仍未得到充分表征。在本研究中，我们报告称，在小鼠大脑海马体CA1区域敲低hnRNPM会导致学习和记忆障碍。突触素和PSD95这两种突触前和突触后蛋白水平的降低进一步支持了这一发现。值得注意的是，hnRNPM的缺失通过损害树突棘的形态影响体内的生理性棘突。此外，我们的研究表明，hnRNPM直接结合突触素和PSD95 mRNA的3'UTR，从而使这些mRNA稳定。总之，这些发现为hnRNPM在神经元结构和功能中的调控作用提供了新的见解。
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