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长链非编码RNA在小鼠大脑中的时空表达及转录扰动

Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain.

作者信息

Goff Loyal A, Groff Abigail F, Sauvageau Martin, Trayes-Gibson Zachary, Sanchez-Gomez Diana B, Morse Michael, Martin Ryan D, Elcavage Lara E, Liapis Stephen C, Gonzalez-Celeiro Meryem, Plana Olivia, Li Eric, Gerhardinger Chiara, Tomassy Giulio S, Arlotta Paola, Rinn John L

出版信息

Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):6855-62. doi: 10.1073/pnas.1411263112.

Abstract

Long noncoding RNAs (lncRNAs) have been implicated in numerous cellular processes including brain development. However, the in vivo expression dynamics and molecular pathways regulated by these loci are not well understood. Here, we leveraged a cohort of 13 lncRNAnull mutant mouse models to investigate the spatiotemporal expression of lncRNAs in the developing and adult brain and the transcriptome alterations resulting from the loss of these lncRNA loci. We show that several lncRNAs are differentially expressed both in time and space, with some presenting highly restricted expression in only selected brain regions. We further demonstrate altered regulation of genes for a large variety of cellular pathways and processes upon deletion of the lncRNA loci. Finally, we found that 4 of the 13 lncRNAs significantly affect the expression of several neighboring proteincoding genes in a cis-like manner. By providing insight into the endogenous expression patterns and the transcriptional perturbations caused by deletion of the lncRNA locus in the developing and postnatal mammalian brain, these data provide a resource to facilitate future examination of the specific functional relevance of these genes in neural development, brain function, and disease.

摘要

长链非编码RNA(lncRNAs)已被证明参与包括大脑发育在内的众多细胞过程。然而,这些基因座所调控的体内表达动态和分子途径尚未得到充分了解。在这里,我们利用一组13个lncRNA基因敲除突变小鼠模型,研究lncRNAs在发育中和成年大脑中的时空表达,以及这些lncRNA基因座缺失导致的转录组改变。我们发现,几种lncRNAs在时间和空间上均有差异表达,其中一些仅在特定脑区呈现高度受限的表达。我们进一步证明,lncRNA基因座缺失后,多种细胞途径和过程的基因调控发生改变。最后,我们发现13个lncRNAs中有4个以顺式样方式显著影响几个相邻蛋白质编码基因的表达。通过深入了解发育中和出生后哺乳动物大脑中lncRNA基因座缺失所引起的内源性表达模式和转录扰动,这些数据为促进未来研究这些基因在神经发育、脑功能和疾病中的特定功能相关性提供了资源。

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