Deciphering the Functional Long Non-Coding RNAs Derived from MicroRNA Loci.

Deciphering the Functional Long Non-Coding RNAs Derived from MicroRNA Loci.
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DOI:
10.1002/advs.202203987
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发表时间:
2023-11
期刊:
影响因子:
15.1
通讯作者:
Wang, Fang
Wang, Fang
中科院分区:
材料科学1区
文献类型:
--
作者:
Li, Weiqian;Huo, Yue;Ren, Yue;Han, Chenxi;Li, Shuo;Wang, Kangning;He, Manman;Chen, Yiying;Wang, Yanran;Xu, Lingjie;Guo, Yuehong;Si, Yanmin;Gao, Yufeng;Xu, Jiayue;Wang, Xiaoshuang;Ma, Yanni;Yu, Jia;Wang, Fang

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尽管大多数真核生物的基因组可以普遍转录成不同的lncRNA群体,但也发现了不同亚型的lncRNA。然而,对miRNA来源的lncRNAs的全基因组研究仍然缺乏。据报道,有800多个miRNA基因起源的lncRNAs(MolncRNAs)是由miRNA基因座产生的。其中一种是来自miR-301b和miR-130b的molnc-301b,其功能是作为“RNA诱饵”,促进染色质重塑蛋白SMARCA5从染色质中解离,从而隔离转录和mRNA翻译。具体地说,Molnc-301b通过抑制红细胞生成和翻译相关基因的转录,如GATA1和FOS,来减弱红细胞生成。此外,还建立了一个实用而强大的CRISPR筛选平台,用于在大规模和单细胞水平上鉴定MolncRNAs的生物学功能,并鉴定了29个在造血细胞中具有功能的MolncRNAs。总的来说,重点放在miRNA衍生的lncRNAs上,破译它们在正常造血过程中的情况,并全面评估它们的潜在作用。这项工作全面地描述了860多个miRNA基因起源的lncRNAs(MolncRNAs),并阐明了它们在红细胞生成过程中的情况。其中之一,Molnc-301b,通过协调关键的红系调节因子的转录和翻译效率,独立于其同源miRNAs调节红系分化。最后,建立了一个基于CRISPR的单细胞RNA测序的筛选平台,以在大规模和单细胞水平上对功能性MolncRNAs进行表征。
Albeit the majority of eukaryotic genomes can be pervasively transcribed to a diverse population of lncRNAs and various subtypes of lncRNA are discovered. However, the genome‐wide study of miRNA‐derived lncRNAs is still lacking. Here, it is reported that over 800 miRNA gene‐originated lncRNAs (molncRNAs) are generated from miRNA loci. One of them, molnc‐301b from miR‐301b and miR‐130b, functions as an “RNA decoy” to facilitate dissociation of the chromatin remodeling protein SMARCA5 from chromatin and thereby sequester transcription and mRNA translation. Specifically, molnc‐301b attenuates erythropoiesis by mitigating the transcription of erythropoietic and translation‐associated genes, such as GATA1 and FOS. In addition, a useful and powerful CRISPR screen platform to characterize the biological functions of molncRNAs at large‐scale and single‐cell levels is established and 29 functional molncRNAs in hematopoietic cells are identified. Collectively, the focus is on miRNA‐derived lncRNAs, deciphering their landscape during normal hematopoiesis, and comprehensively evaluating their potential roles. This work comprehensively characterizes over 860 miRNA gene‐originated lncRNAs (molncRNAs) and clarifies their landscape during erythropoiesis. One of them, molnc‐301b, regulates erythroid differentiation independent of its cognate miRNAs by coordinating the transcription and translation efficiency of key erythroid regulators. Finally, a screening platform using CRISPR‐based single‐cell RNA sequencing is established to characterize functional molncRNAs at large‐scale and single‐cell levels.
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