日本研究人员在最新一期《自然—神经科学》杂志网络版上发表论文说,他们在利用实验鼠进行的实验中,发现一种小核糖核酸与脑神经和视网膜神经的形成有关。这是世界上首次发现小核糖核酸参与神经线路的形成,将有助于弄清癫痫和自闭症等疾病的原因。
小核糖核酸是一类不编码制造蛋白质的单链核糖核酸分子,主要参与控制基因表达。
日本大阪生物科学研究所、名古屋大学和京都大学研究人员组成的联合研究小组发现,在脑内,小核糖核酸-124a的含量很高。于是他们培育了使脑内小核糖核酸-124a不再发挥作用的实验鼠,并进行分析。结果发现,实验鼠的脑变小了,脑内与记忆有关的海马区的神经细胞与通常情况下本不应结合在一起的神经细胞结合起来,神经线路因此出现异常。而在视网膜中,与视力和色觉有关的神经细胞也死亡了。
研究小组进一步发现,在实验鼠脑发育过程中发挥作用、但应随着脑成熟而不再发挥作用的Lhx2基因在上述实验鼠的脑内却一直发挥作用。研究小组认为,这是因小核糖核酸-124a不再发挥作用,使Lhx2基因不再受到遏制,从而导致神经异常。(生物谷 Bioon.com)
doi:10.1038/nn.2897
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miR-124a is required for hippocampal axogenesis and retinal cone survival through Lhx2 suppression
Rikako Sanuki; Akishi Onishi; Chieko Koike; Rieko Muramatsu; Satoshi Watanabe; Yuki Muranishi; Shoichi Irie; Shinji Uneo; Toshiyuki Koyasu; Ryosuke Matsui; Yoan Chérasse; Yoshihiro Urade; Dai Watanabe; Mineo Kondo; Toshihide Yamashita; Takahisa Furukawa
MicroRNA-124a (miR-124a) is the most abundant microRNA expressed in the vertebrate CNS. Despite past investigations into the role of miR-124a, inconsistent results have left the in vivo function of miR-124a unclear. We examined the in vivo function of miR-124a by targeted disruption of Rncr3 (retinal non-coding RNA 3), the dominant source of miR-124a. Rncr3−/− mice exhibited abnormalities in the CNS, including small brain size, axonal mis-sprouting of dentate gyrus granule cells and retinal cone cell death. We found that Lhx2 is an in vivo target mRNA of miR-124a. We also observed that LHX2 downregulation by miR-124a is required for the prevention of apoptosis in the developing retina and proper axonal development of hippocampal neurons. These results suggest that miR-124a is essential for the maturation and survival of dentate gyrus neurons and retinal cones, as it represses Lhx2 translation.