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白鱼中与微囊藻毒素-LR诱导的肝损伤相关的长链非编码RNA的从头分析:发现与展望

De Novo Profiling of Long Non-Coding RNAs Involved in MC-LR-Induced Liver Injury in Whitefish: Discovery and Perspectives.

作者信息

Florczyk Maciej, Brzuzan Paweł, Woźny Maciej

机构信息

Department of Environmental Biotechnology, Faculty of Geoengineering, University of Warmia and Mazury in Olsztyn, ul. Słoneczna 45G, 10-709 Olsztyn, Poland.

出版信息

Int J Mol Sci. 2021 Jan 19;22(2):941. doi: 10.3390/ijms22020941.

Abstract

Microcystin-LR (MC-LR) is a potent hepatotoxin for which a substantial gap in knowledge persists regarding the underlying molecular mechanisms of liver toxicity and injury. Although long non-coding RNAs (lncRNAs) have been extensively studied in model organisms, our knowledge concerning the role of lncRNAs in liver injury is limited. Given that lncRNAs show low levels of sequence conservation, their role becomes even more unclear in non-model organisms without an annotated genome, like whitefish (). The objective of this study was to discover and profile aberrantly expressed polyadenylated lncRNAs that are involved in MC-LR-induced liver injury in whitefish. Using RNA sequencing (RNA-Seq) data, we de novo assembled a high-quality whitefish liver transcriptome. This enabled us to find 94 differentially expressed (DE) putative evolutionary conserved lncRNAs, such as MALAT1, HOTTIP, HOTAIR or HULC, and 4429 DE putative novel whitefish lncRNAs, which differed from annotated protein-coding transcripts (PCTs) in terms of minimum free energy, guanine-cytosine (GC) base-pair content and length. Additionally, we identified DE non-coding transcripts that might be 3' autonomous untranslated regions (3'UTRs) of mRNAs. We found both evolutionary conserved lncRNAs as well as novel whitefish lncRNAs that could serve as biomarkers of liver injury.

摘要

微囊藻毒素-LR(MC-LR)是一种强效肝毒素,关于其肝毒性和损伤的潜在分子机制,目前仍存在相当大的知识空白。尽管长链非编码RNA(lncRNA)已在模式生物中得到广泛研究,但我们对lncRNA在肝损伤中的作用了解有限。鉴于lncRNA的序列保守性较低,在没有注释基因组的非模式生物(如白鲑)中,它们的作用变得更加不明确。本研究的目的是发现并分析参与MC-LR诱导白鲑肝损伤的异常表达的多聚腺苷酸化lncRNA。利用RNA测序(RNA-Seq)数据,我们从头组装了高质量的白鲑肝脏转录组。这使我们能够找到94个差异表达(DE)的假定进化保守lncRNA,如MALAT1、HOTTIP、HOTAIR或HULC,以及4429个DE假定的新型白鲑lncRNA,它们在最小自由能、鸟嘌呤-胞嘧啶(GC)碱基对含量和长度方面与注释的蛋白质编码转录本(PCT)不同。此外,我们还鉴定出可能是mRNA的3'自主非翻译区(3'UTR)的DE非编码转录本。我们发现进化保守的lncRNA以及新型白鲑lncRNA都可作为肝损伤的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97ba/7833382/bf3f421a718f/ijms-22-00941-g001.jpg

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