Molecular roles and function of circular RNAs in eukaryotic cells.

Molecular roles and function of circular RNAs in eukaryotic cells.
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DOI:
10.1007/s00018-017-2688-5
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发表时间:
2018-03
期刊:
Cellular and molecular life sciences : CMLS
影响因子:
--
通讯作者:
Teupser D
Teupser D
中科院分区:
其他
文献类型:
--
作者:
Holdt LM;Kohlmaier A;Teupser D

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真核生物中的蛋白质编码基因和非编码基因通常表达为线性信使RNA,外显子与其基因组顺序共线排列。在测序和将RNA读数映射到参考基因组中的最新进展已经揭示了数千个基因也表达共价闭合的环状RNA。这些circRNA中的许多是稳定的并且含有外显子,但不翻译成蛋白质。在这里,我们回顾了新出现的理解,这两个,circRNA产生的共和转录后的头到尾的“回剪接”的下游剪接供体到一个更上游的剪接受体,以及circRNA产生的内含子lariats共线剪接过程中,可能会表现出生理相关的调节功能,在真核生物。我们描述了circRNA如何通过影响转录起始和延伸或剪接来影响其宿主基因位点的基因表达,以及它们如何参与控制其他分子的功能,例如通过与microRNA和蛋白质相互作用。最后,我们展望了circRNA失调如何影响疾病,以及circRNA的稳定性如何在生物医学应用中被利用。
Protein-coding and noncoding genes in eukaryotes are typically expressed as linear messenger RNAs, with exons arranged colinearly to their genomic order. Recent advances in sequencing and in mapping RNA reads to reference genomes have revealed that thousands of genes express also covalently closed circular RNAs. Many of these circRNAs are stable and contain exons, but are not translated into proteins. Here, we review the emerging understanding that both, circRNAs produced by co- and posttranscriptional head-to-tail “backsplicing” of a downstream splice donor to a more upstream splice acceptor, as well as circRNAs generated from intronic lariats during colinear splicing, may exhibit physiologically relevant regulatory functions in eukaryotes. We describe how circRNAs impact gene expression of their host gene locus by affecting transcriptional initiation and elongation or splicing, and how they partake in controlling the function of other molecules, for example by interacting with microRNAs and proteins. We conclude with an outlook how circRNA dysregulation affects disease, and how the stability of circRNAs might be exploited in biomedical applications.
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