当前位置: X-MOL 学术Cell Death Discov. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Temporal transcriptome analysis of neuronal commitment reveals the preeminent role of the divergent lncRNA biotype and a critical candidate gene during differentiation.
Cell Death Discovery ( IF 7 ) Pub Date : 2020-04-24 , DOI: 10.1038/s41420-020-0263-6
Bharat Prajapati 1 , Mahar Fatima 1 , Mena Fatma 1 , Priya Maddhesiya 1 , Himali Arora 1 , Teesta Naskar 1 , Subhashree Devasenapathy 1 , Pankaj Seth 1 , Subrata Sinha 1, 2
Affiliation  

lncRNA genes can be genic or "intergenic". "Genic" RNAs can be further divided into six biotypes. Through genome-wide analysis of a publicly available data set on corticogenesis, we found that the divergent lncRNA (XH) biotype, comprising the lncRNA and the coding gene being in opposite directions in a head-to-head manner, was most prominent during neural commitment. Within this biotype, a coding gene/divergent RNA pair of the BASP1 gene and the uncharacterized RNA loc285696 (hitherto referred as BASP1-AS1) formed a major HUB gene during neuronal differentiation. Experimental validation during the in vitro differentiation of human neural progenitor cells (hNPCs) showed that BASP1-AS1 regulates the expression of its adjacent coding gene, BASP1. Both transcripts increased sharply on the first day of neuronal differentiation of hNPCs, to fall steadily thereafter, reaching very low levels in differentiated neurons. BASP1-AS1 RNA and the BASP1 gene formed a molecular complex that also included the transcription factor TCF12. TCF12 is coded by the DYX1 locus, associated with inherited dyslexia and neurodevelopmental defects. Knockdown of BASP1-AS1, BASP1, or TCF12 impaired the neuronal differentiation of hNPCs, as seen by reduction in DCX and TUJ1-positive cells and by reduced neurite length. There was also increased cell proliferation. A common set of critical genes was affected by the three molecules in the complex. Our study thus identified the role of the XH biotype and a novel mediator of neuronal differentiation-the complex of BASP1-AS1, BASP1, and TCF12. It also linked a neuronal differentiation pathway to inherited dyslexia.

中文翻译:

神经元定向的时间转录组分析揭示了不同的 lncRNA 生物型和分化过程中关键候选基因的卓越作用。

lncRNA基因可以是基因的或“基因间的”。“基因”RNA 可进一步分为六种生物型。通过对公开的皮质生成数据集进行全基因组分析,我们发现不同的 lncRNA (XH) 生物型,包括头对头方向相反的 lncRNA 和编码基因,在神经元发育过程中最为突出。承诺。在该生物型中,BASP1 基因的编码基因/分歧 RNA 对和未表征的 RNA loc285696(迄今为止称为 BASP1-AS1)在神经元分化过程中形成了主要的 HUB 基因。人神经祖细胞 (hNPC) 体外分化期间的实验验证表明,BASP1-AS1 调节其相邻编码基因 BASP1 的表达。两种转录本在 hNPC 神经元分化的第一天急剧增加,此后稳步下降,在分化的神经元中达到非常低的水平。BASP1-AS1 RNA 和 BASP1 基因形成分子复合物,其中还包括转录因子 TCF12。TCF12 由 DYX1 位点编码,与遗传性阅读障碍和神经发育缺陷相关。BASP1-AS1、BASP1 或 TCF12 的敲低会损害 hNPC 的神经元分化,如 DCX 和 TUJ1 阳性细胞的减少以及神经突长度的减少所示。细胞增殖也增加。一组常见的关键基因受到复合物中三个分子的影响。因此,我们的研究确定了 XH 生物型和神经元分化的新型介质 - BASP1-AS1、BASP1 和 TCF12 复合体的作用。它还将神经元分化途径与遗传性阅读障碍联系起来。
更新日期:2020-04-24
down
wechat
bug