State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Haihe Laboratory of Cell Ecosystem, The Key Laboratory of RNA and Hematopoietic Regulation, Chinese Academy of Medical Sciences / Peking Union Medical College, Beijing, 100005, P.R. China.
Emergency Department of West China Hospital, Sichuan University, Chengdu, 610041, P.R. China.
Adv Sci (Weinh). 2023 Nov;10(33):e2203987. doi: 10.1002/advs.202203987. Epub 2023 Oct 17.
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.
尽管大多数真核基因组可以广泛转录为多种长链非编码 RNA（lncRNA），并且发现了各种亚型的 lncRNA，但 miRNA 衍生的 lncRNA 的全基因组研究仍然缺乏。在这里，据报道，超过 800 个 miRNA 基因起源的 lncRNA（molncRNA）是从 miRNA 基因座产生的。其中之一，来自 miR-301b 和 miR-130b 的 molnc-301b，作为一种“RNA 诱饵”，促进染色质重塑蛋白 SMARCA5 从染色质上解离，从而隔离转录和 mRNA 翻译。具体来说，molnc-301b 通过减轻红细胞生成和翻译相关基因（如 GATA1 和 FOS）的转录来抑制红细胞生成。此外，建立了一个有用的和强大的 CRISPR 筛选平台，以在大规模和单细胞水平上表征 molncRNA 的生物学功能，并鉴定了造血细胞中的 29 个功能 molncRNA。总之，重点是 miRNA 衍生的 lncRNA，阐明它们在正常造血过程中的特征，并全面评估它们的潜在作用。
