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LINE-1反转录转座子有助于小鼠PV中间神经元的发育
作者:小柯机器人 发布时间:2024/5/26 17:52:04

澳大利亚昆士兰大学Geoffrey J. Faulkner等研究人员合作发现,LINE-1反转录转座子有助于小鼠PV中间神经元的发育。2024年5月21日,《自然—神经科学》杂志在线发表了这项成果。

研究人员报告了SOX6对LINE-1(L1)的程序性激活,SOX6是一种对小清蛋白(PV)中间神经元发育至关重要的转录因子。小鼠PV中间神经元允许L1在体外和体内动员,携带未甲基化的L1启动子,并表达全长的L1 mRNA和蛋白质。
 
利用纳米孔长读序测序技术,研究人员发现了PV中间神经元基因近端未甲基化的L1,包括一种新型的L1启动子驱动的Caps2转录本亚型,它能增强体外神经元形态的复杂性。这些数据凸显了L1顺式调控元件对PV中间神经元发育和转录组多样性所做的贡献,L1在这种环境中的流动性揭示了这一点。

据悉,反转录转座子是通过RNA中间体的转录和反转录复制的移动DNA序列。反转录转座子编码的顺式调节元件还能促进相邻基因的转录。在哺乳动物神经元中发现了体细胞L1反转录转座子插入。然而,目前还不清楚L1序列是否只在某些神经元谱系中移动,还是在其中促进神经发育基因的表达。

附:英文原文

Title: LINE-1 retrotransposons contribute to mouse PV interneuron development

Author: Bodea, Gabriela O., Botto, Juan M., Ferreiro, Maria E., Sanchez-Luque, Francisco J., de los Rios Barreda, Jose, Rasmussen, Jay, Rahman, Muhammed A., Fenlon, Laura R., Jansz, Natasha, Gubert, Carolina, Gerdes, Patricia, Bodea, Liviu-Gabriel, Ajjikuttira, Prabha, Da Costa Guevara, Darwin J., Cumner, Linda, Bell, Charles C., Kozulin, Peter, Billon, Victor, Morell, Santiago, Kempen, Marie-Jeanne H. C., Love, Chloe J., Saha, Karabi, Palmer, Lucy M., Ewing, Adam D., Jhaveri, Dhanisha J., Richardson, Sandra R., Hannan, Anthony J., Faulkner, Geoffrey J.

Issue&Volume: 2024-05-21

Abstract: Retrotransposons are mobile DNA sequences duplicated via transcription and reverse transcription of an RNA intermediate. Cis-regulatory elements encoded by retrotransposons can also promote the transcription of adjacent genes. Somatic LINE-1 (L1) retrotransposon insertions have been detected in mammalian neurons. It is, however, unclear whether L1 sequences are mobile in only some neuronal lineages or therein promote neurodevelopmental gene expression. Here we report programmed L1 activation by SOX6, a transcription factor critical for parvalbumin (PV) interneuron development. Mouse PV interneurons permit L1 mobilization in vitro and in vivo, harbor unmethylated L1 promoters and express full-length L1 mRNAs and proteins. Using nanopore long-read sequencing, we identify unmethylated L1s proximal to PV interneuron genes, including a novel L1 promoter-driven Caps2 transcript isoform that enhances neuron morphological complexity in vitro. These data highlight the contribution made by L1 cis-regulatory elements to PV interneu

DOI: 10.1038/s41593-024-01650-2

Source: https://www.nature.com/articles/s41593-024-01650-2

期刊信息

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新IF:28.771
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex