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长链非编码RNA下调老年雄性大鼠黑质中Myh1、Casr和Mis18a的表达。

LncRNAs down-regulate Myh1, Casr, and Mis18a expression in the Substantia Nigra of aged male rats.

作者信息

Zhang Guoliang, Kang Yunxiao, Feng Xu, Cui Rui, Guo Qiqing, Ji Xiaoming, Huang Yuanxiang, Ma Yannan, Liu Shufeng, Shi Geming

机构信息

Department of Neurobiology, Hebei Medical University, Hebei Province, Shijiazhuang, 050017, China.

Department of Human Anatomy, Hebei Medical University, Hebei Province, Shijiazhuang, 050017, China.

出版信息

Aging (Albany NY). 2019 Oct 2;11(19):8313-8328. doi: 10.18632/aging.102321.

DOI:10.18632/aging.102321
PMID:31576812
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6814601/
Abstract

In this study, we used high-throughput RNA sequencing to identify mRNAs, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) that are differentially expressed in the Substantia Nigra (SN) of aged and young rats. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to perform functional annotation of mRNAs that were either differentially expressed themselves (DEMs), targeted by differentially expressed lncRNAs (DELs), or the parents of differentially expressed circRNAs (DECs). A total of 112 DEMs, 163 DELs, and 98 DECs were found in the SN of aged rats. The down-regulated lncRNA NONRATT010417.2 targeted the down-regulated mRNA Myh1, while the down-regulated lncRNA NONRATT015586.2 and the up-regulated lncRNAs NONRATT000490.2 and NONRATT007029.2 all targeted the down-regulated mRNAs Casr and Mis18a. Western blots and RT-qPCR revealed that Myh1, Casr, and Mis18a protein and mRNA expression were significantly reduced in aged rats compared to young rats. This study improves our understanding of the transcriptional alterations underlying aging-related changes in the SN and provides a foundation for future studies of associated molecular mechanisms.

摘要

在本研究中，我们使用高通量RNA测序来鉴定在老年和年轻大鼠黑质（SN）中差异表达的mRNA、长链非编码RNA（lncRNA）和环状RNA（circRNA）。基因本体论和京都基因与基因组百科全书通路分析用于对差异表达的mRNA（DEM）、差异表达的lncRNA（DEL）靶向的mRNA或差异表达的circRNA（DEC）的亲本进行功能注释。在老年大鼠的黑质中总共发现了112个DEM、163个DEL和98个DEC。下调的lncRNA NONRATT010417.2靶向下调的mRNA Myh1，而下调的lncRNA NONRATT015586.2以及上调的lncRNAs NONRATT000490.2和NONRATT007029.2均靶向下调的mRNA Casr和Mis18a。蛋白质免疫印迹和逆转录定量PCR显示，与年轻大鼠相比，老年大鼠中Myh1、Casr和Mis18a的蛋白质和mRNA表达显著降低。本研究增进了我们对黑质衰老相关变化背后转录改变的理解，并为未来相关分子机制的研究奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/458a/6814601/e690a9f45c92/aging-11-102321-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/458a/6814601/57dbb58499a1/aging-11-102321-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/458a/6814601/e378cbb8bec9/aging-11-102321-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/458a/6814601/f3fb6ed738df/aging-11-102321-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/458a/6814601/cda035925ad3/aging-11-102321-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/458a/6814601/4a4abbc7b154/aging-11-102321-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/458a/6814601/83c4e6558d84/aging-11-102321-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/458a/6814601/e690a9f45c92/aging-11-102321-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/458a/6814601/57dbb58499a1/aging-11-102321-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/458a/6814601/e378cbb8bec9/aging-11-102321-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/458a/6814601/f3fb6ed738df/aging-11-102321-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/458a/6814601/cda035925ad3/aging-11-102321-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/458a/6814601/4a4abbc7b154/aging-11-102321-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/458a/6814601/83c4e6558d84/aging-11-102321-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/458a/6814601/e690a9f45c92/aging-11-102321-g007.jpg

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Atypical nested 22q11.2 duplications between LCR22B and LCR22D are associated with neurodevelopmental phenotypes including autism spectrum disorder with incomplete penetrance.LCR22B和LCR22D之间非典型的嵌套22q11.2重复与神经发育表型相关，包括具有不完全外显率的自闭症谱系障碍。
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