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Targeting a Long Non-Coding RNA splicing by novel candidate drug ABX464 to produce the anti-inflammatory microRNA miR-124
bioRxiv - Immunology Pub Date : 2020-05-30 , DOI: 10.1101/2019.12.11.871335
Laurent Manchon , Audrey Vautrin , Jamal Tazi , Aude Garcel , Noelie Campos

Many nascent long non-coding RNAs have received considerable attention in recent years because of their major regulatory roles in gene expression and signaling pathways at various levels. Indeed long non-coding RNAs undergo the same maturation steps as pre-mRNAs of protein- coding genes, but they are less efficiently spliced and polyadenylated in comparison to them. Here we focus on a specific human long non-coding RNA and we show the activity of a new candidate drug that potentially affect its splicing and generate an anti-HIV and anti-inflammatory effects driven by upregulation of microRNA biogenesis. To investigate this activity we combine the use of capture sequencing technology and an ab initio transcript assembly on cells from six healthy individuals. The sequencing depth of capture sequencing permitted us to assemble transcripts exhibiting a complex array of splicing patterns. In essence, we revealed that splicing of the long non-coding RNA is greatly increased by the drug whereas this splicing is less represented in untreated samples.

中文翻译:

针对新型候选药物ABX464的长非编码RNA剪接产生抗炎microRNA miR-124

近年来,许多新生的长非编码RNA受到了广泛关注,因为它们在不同水平的基因表达和信号通路中起着重要的调节作用。确实,长的非编码RNA与蛋白质编码基因的前mRNA经历相同的成熟步骤,但是与它们相比,它们的剪接和聚腺苷酸化效率较低。在这里,我们着眼于特定的人类长非编码RNA,我们展示了一种新的候选药物的活性,该活性可能影响其剪接并产生由微RNA生物发生上调驱动的抗HIV和抗炎作用。为了调查这项活动,我们将捕获测序技术的使用与六个健康个体的细胞的从头转录本组装相结合。捕获测序的测序深度允许我们组装表现出复杂拼接模式阵列的转录本。从本质上讲,我们发现长非编码RNA的剪接被药物大大增加了,而这种剪接在未处理的样品中代表较少。
更新日期:2020-05-30
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