Ling King-Hwa, Brautigan Peter J, Moore Sarah, Fraser Rachel, Cheah Pike-See, Raison Joy M, Babic Milena, Lee Young Kyung, Daish Tasman, Mattiske Deidre M, Mann Jeffrey R, Adelson David L, Thomas Paul Q, Hahn Christopher N, Scott Hamish S
Department of Molecular Pathology, The Institute of Medical and Veterinary Science and The Hanson Institute, P.O. Box 14 Rundle Mall Post Office, Adelaide, SA 5000, Australia; School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, SA 5005, Australia; NeuroBiology & Genetics Group, Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor DE, Malaysia.
Department of Molecular Pathology, The Institute of Medical and Veterinary Science and The Hanson Institute, P.O. Box 14 Rundle Mall Post Office, Adelaide, SA 5000, Australia.
Genomics. 2016 Mar;107(2-3):88-99. doi: 10.1016/j.ygeno.2016.01.006. Epub 2016 Jan 21.
Natural antisense transcripts (NATs) are involved in cellular development and regulatory processes. Multiple NATs at the Sox4 gene locus are spatiotemporally regulated throughout murine cerebral corticogenesis. In the study, we evaluated the potential functional role of Sox4 NATs at Sox4 gene locus. We demonstrated Sox4 sense and NATs formed dsRNA aggregates in the cytoplasm of brain cells. Over expression of Sox4 NATs in NIH/3T3 cells generally did not alter the level of Sox4 mRNA expression or protein translation. Upregulation of a Sox4 NAT known as Sox4ot1 led to the production of a novel small RNA, Sox4_sir3. Its biogenesis is Dicer1-dependent and has characteristics resemble piRNA. Expression of Sox4_sir3 was observed in the marginal and germinative zones of the developing and postnatal brains suggesting a potential role in regulating neurogenesis. We proposed that Sox4 sense-NATs serve as Dicer1-dependent templates to produce a novel endo-siRNA- or piRNA-like Sox4_sir3.
天然反义转录本(NATs)参与细胞发育和调控过程。Sox4基因位点的多个NATs在小鼠大脑皮质发生过程中受到时空调控。在本研究中,我们评估了Sox4基因位点处Sox4 NATs的潜在功能作用。我们证明Sox4正义链和NATs在脑细胞的细胞质中形成双链RNA聚集体。在NIH/3T3细胞中过表达Sox4 NATs通常不会改变Sox4 mRNA表达水平或蛋白质翻译。一种名为Sox4ot1的Sox4 NAT的上调导致了一种新型小RNA即Sox4_sir3的产生。其生物合成依赖于Dicer1,并且具有类似于piRNA的特征。在发育中和出生后大脑的边缘区和生发区观察到了Sox4_sir3的表达,提示其在调节神经发生中可能发挥作用。我们提出Sox4正义链-NATs作为依赖于Dicer1的模板来产生一种新型的内源性小干扰RNA样或piRNA样的Sox4_sir3。