全基因组鉴定新型长非编码 RNA 及其在缺氧斑马鱼脑内的可能作用

Genome-wide identification of novel long non-coding RNAs and their possible roles in hypoxic zebrafish brain.

机构信息

Musculoskeletal Genetics Laboratory, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel.

Biochemical Adaptation Laboratory, Department of Zoology, North-Eastern Hill University, Shillong 793022, India.

出版信息

Genomics. 2021 Jan;113(1 Pt 1):29-43. doi: 10.1016/j.ygeno.2020.11.023. Epub 2020 Nov 29.

DOI:10.1016/j.ygeno.2020.11.023

PMID:33264657

Abstract

Long non-coding RNAs (lncRNAs) are the master regulators of numerous biological processes. Hypoxia causes oxidative stress with severe and detrimental effects on brain function and acts as a critical initiating factor in the pathogenesis of Alzheimer's disease (AD). From the RNA-Seq in the forebrain (Fb), midbrain (Mb), and hindbrain (Hb) regions of hypoxic and normoxic zebrafish, we identified novel lncRNAs, whose potential cis targets showed involvement in neuronal development and differentiation pathways. Under hypoxia, several lncRNAs and mRNAs were differentially expressed. Co-expression studies indicated that the Fb and Hb regions' potential lncRNA target genes were involved in the AD pathogenesis. In contrast, those in Mb (cry1b, per1a, cipca) was responsible for regulating circadian rhythm. We identified specific lncRNAs present in the syntenic regions between zebrafish and humans, possibly functionally conserved. We thus identified several conserved lncRNAs as the probable regulators of AD genes (adrb3b, cav1, stat3, bace2, apoeb, psen1, s100b).

摘要

长链非编码 RNA（lncRNAs）是许多生物过程的主要调节因子。缺氧会导致氧化应激，对大脑功能产生严重的不利影响，并作为阿尔茨海默病（AD）发病机制的关键起始因素。通过对缺氧和正常氧斑马鱼的前脑（Fb）、中脑（Mb）和后脑（Hb）区域的 RNA-Seq 分析，我们鉴定了新的 lncRNAs，其潜在的顺式靶标参与了神经元发育和分化途径。在缺氧条件下，一些 lncRNAs 和 mRNAs 表达差异。共表达研究表明，Fb 和 Hb 区域的潜在 lncRNA 靶基因参与了 AD 的发病机制。相比之下，Mb（cry1b、per1a、cipca）中的那些则负责调节昼夜节律。我们鉴定了在斑马鱼和人类之间的同源区域存在的特定 lncRNAs，可能具有功能保守性。因此，我们鉴定了一些保守的 lncRNAs 作为 AD 基因（adrb3b、cav1、stat3、bace2、apoeb、psen1、s100b）的可能调节因子。