Are Argonaute-Associated Tiny RNAs Junk, Inferior miRNAs, or a New Type of Functional RNAs?

Are Argonaute-Associated Tiny RNAs Junk, Inferior miRNAs, or a New Type of Functional RNAs?
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DOI:
10.3389/fmolb.2021.795356
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发表时间:
2021
影响因子:
5
通讯作者:
Nakanishi K
Nakanishi K
中科院分区:
生物学3区
文献类型:
--
作者:
Nakanishi K

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microRNAs (miRNAs)的生物合成途径已经被很好地表征,并确定了所需的组分。miRNA是由miRNA基因和其他rna的转录本合成的,如内含子、转移rna、核糖体rna、小核仁rna,甚至是病毒miRNA。这些小rna被装载到Argonaute (AGO)蛋白中,招募效应复合物靶向mrna,在转录后抑制其基因表达。虽然成熟的mirna被定义为19 - 23个核苷酸(nt),但研究发现,与全长成熟mirna相比,短于19个核苷酸的微小rna (tyRNAs)与AGOs结合的miRNAs数量相等或更少。相比之下,我最近的研究表明,当人类AGO3装载14nt切割诱导tyrna (cityRNAs)时,它可以成为与AGO2相当的切片器,这些tyrna由相应成熟miRNA的前14nt组成。这一观察结果提出了tyrna与其成熟形式起不同作用的可能性。这篇综述主要关注于人类短于19 nt的AGO相关tyrna,并讨论了它们可能的生物合成途径和生理益处,包括tyrna如何避免靶向性miRNA降解伴随AGO多泛素化。
The biosynthesis pathways of microRNAs (miRNAs) have been well characterized with the identification of the required components. miRNAs are synthesized from the transcripts of miRNA genes and other RNAs, such as introns, transfer RNAs, ribosomal RNAs, small nucleolar RNAs, and even viral miRNAs. These small RNAs are loaded into Argonaute (AGO) proteins and recruit the effector complexes to target mRNAs, repressing their gene expression post-transcriptionally. While mature miRNAs were defined as 19–23 nucleotides (nt), tiny RNAs (tyRNAs) shorter than 19 nt have been found to bind AGOs as equivalent or lesser miRNAs compared to their full-length mature miRNAs. In contrast, my recent study revealed that when human AGO3 loads 14 nt cleavage-inducing tyRNAs (cityRNAs), comprised of the first 14 nt of their corresponding mature miRNA, it can become a comparable slicer to AGO2. This observation raises the possibility that tyRNAs play distinct roles from their mature form. This minireview focuses on human AGO-associated tyRNAs shorter than 19 nt and discusses their possible biosynthesis pathways and physiological benefits, including how tyRNAs could avoid target-directed miRNA degradation accompanied by AGO polyubiquitination.
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