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从果蝇的异染色质到长链非编码RNA:拓展基因功能与调控的领域

From Heterochromatin to Long Noncoding RNAs in Drosophila: Expanding the Arena of Gene Function and Regulation.

作者信息

Lakhotia Subhash C

机构信息

Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, 221005, India.

出版信息

Adv Exp Med Biol. 2017;1008:75-118. doi: 10.1007/978-981-10-5203-3_3.

DOI:10.1007/978-981-10-5203-3_3
PMID:28815537
Abstract

Recent years have witnessed a remarkable interest in exploring the significance of pervasive noncoding transcripts in diverse eukaryotes. Classical cytogenetic studies using the Drosophila model system unraveled the perplexing attributes and "functions" of the "gene"-poor heterochromatin. Recent molecular studies in the fly model are likewise revealing the very diverse and significant roles played by long noncoding RNAs (lncRNAs) in development, gene regulation, chromatin organization, cell and nuclear architecture, etc. There has been a rapid increase in the number of identified lncRNAs, although a much larger number still remains unknown. The diversity of modes of actions and functions of the limited number of Drosophila lncRNAs, which have been examined, already reflects the profound roles of such RNAs in generating and sustaining the biological complexities of eukaryotes. Several of the known Drosophila lncRNAs originate as independent sense or antisense transcripts from promoter or intergenic, intronic, or 5'/3'-UTR regions, while many of them are independent genes that produce only lncRNAs or coding as well as noncoding RNAs. The different lncRNAs affect chromatin organization (local or large-scale pan-chromosomal), transcription, RNA processing/stability, or translation either directly through interaction with their target DNA sequences or indirectly by acting as intermediary molecules for specific regulatory proteins or may act as decoys/sinks, or storage sites for specific proteins or groups of proteins, or may provide a structural framework for the assembly of substructures in nucleus/cytoplasm. It is interesting that many of the "functions" alluded to heterochromatin in earlier cytogenetic studies appear to find correlates with the known subtle as well as far-reaching actions of the different small and long noncoding RNAs. Further studies exploiting the very rich and powerful genetic and molecular resources available for the Drosophila model are expected to unravel the mystery underlying the long reach of ncRNAs.

摘要

近年来,人们对探索普遍存在的非编码转录本在各种真核生物中的重要性产生了浓厚兴趣。使用果蝇模型系统进行的经典细胞遗传学研究揭示了基因贫乏的异染色质令人困惑的特征和“功能”。果蝇模型中的最新分子研究同样揭示了长链非编码RNA(lncRNA)在发育、基因调控、染色质组织、细胞和核结构等方面发挥的非常多样且重要的作用。已鉴定的lncRNA数量迅速增加,尽管仍有大量lncRNA未知。已研究的有限数量的果蝇lncRNA的作用方式和功能的多样性,已经反映了此类RNA在产生和维持真核生物生物学复杂性方面的深远作用。一些已知的果蝇lncRNA源自启动子或基因间、内含子或5'/3'-UTR区域的独立正义或反义转录本,而其中许多是独立基因,仅产生lncRNA或同时产生编码和非编码RNA。不同的lncRNA通过与靶DNA序列直接相互作用,或作为特定调节蛋白的中间分子间接作用,或作为诱饵/汇聚点、特定蛋白质或蛋白质组的储存位点,或为细胞核/细胞质中亚结构的组装提供结构框架,从而影响染色质组织(局部或大规模全染色体)、转录、RNA加工/稳定性或翻译。有趣的是,早期细胞遗传学研究中提到的异染色质的许多“功能”,似乎与不同的小非编码RNA和长非编码RNA已知的微妙以及深远作用相关。利用果蝇模型中非常丰富和强大的遗传和分子资源进行的进一步研究,有望揭开ncRNA深远影响背后的奥秘。

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