Chen Shangqin, Zhu Jinjin, Li Peijun, Xia Zhaonan, Tu Mengjing, Lin Zhenlang, Xu Baoji, Fu Xiaoqin
The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Department of Neuroscience, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL, 33458, USA.
J Mol Neurosci. 2020 Nov;70(11):1858-1870. doi: 10.1007/s12031-020-01579-8. Epub 2020 May 19.
There are two major isoforms of NTRK2 (neurotrophic receptor tyrosine kinase 2, or TrkB), full-length isoform with tyrosine kinase (TK) domain intact (+) and spliced isoform without tyrosine kinase domain (TK(-)). Within each isoform, there exist subtypes with minor modifications of the protein sequences. In human, the NTRK2 mRNA transcripts encoding TK(+) have same 3'UTRs, while the transcripts encoding subtypes of NTRK2 TK(-) have two completely different 3'UTRs. In mouse, the mRNA transcripts encoding same NTRK2 protein sequence for either TK(+) or TK(-) have long or short 3'UTRs, respectively. The physiological functions of these different 3'UTRs are still unknown. Pilocarpine stimulation increased Ntrk2 mRNA levels in soma, while the increase in synaptosome was smaller. FISH results further showed that mouse Ntrk2 transcripts with different 3'UTRs were distributed differently in cultured cortical neurons. The transcripts with long 3'UTR were distributed more in apical dendrites compared with transcripts with short 3'UTR. Our results provide evidence of non-coding 3'UTR function in regulating mRNA distribution in neurons.
神经营养受体酪氨酸激酶2(NTRK2,即TrkB)有两种主要的亚型,一种是酪氨酸激酶(TK)结构域完整的全长亚型(+),另一种是没有酪氨酸激酶结构域的剪接亚型(TK(-))。在每种亚型中,还存在蛋白质序列有微小修饰的亚型。在人类中,编码TK(+)的NTRK2 mRNA转录本具有相同的3'非翻译区(3'UTR),而编码NTRK2 TK(-)亚型的转录本有两个完全不同的3'UTR。在小鼠中,编码相同NTRK2蛋白质序列的TK(+)或TK(-)的mRNA转录本分别具有长或短的3'UTR。这些不同3'UTR的生理功能仍然未知。毛果芸香碱刺激增加了胞体中Ntrk2 mRNA水平,而突触体中的增加较小。荧光原位杂交(FISH)结果进一步表明,具有不同3'UTR的小鼠Ntrk2转录本在培养的皮层神经元中的分布不同。与具有短3'UTR的转录本相比,具有长3'UTR的转录本在顶端树突中的分布更多。我们的结果为非编码3'UTR在调节神经元mRNA分布中的功能提供了证据。