Long noncoding RNAs: Re-writing dogmas of RNA processing and stability.

Long noncoding RNAs: Re-writing dogmas of RNA processing and stability.
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DOI:
10.1016/j.bbagrm.2015.06.003
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发表时间:
2016-01
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Wilusz JE
Wilusz JE
中科院分区:
其他
文献类型:
--
作者:
Wilusz JE

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大部分人类基因组都是转录的,产生了一个复杂的转录网络,其中包括成千上万的长链非编码rna。许多转录本有一个5 '帽和一个多聚(a)尾,然而一些最丰富的长非编码rna以意想不到的方式加工,缺乏这些规范结构。在这里,我将重点介绍几种具有良好特征的非编码rna产生、稳定和发挥作用的机制。MALAT1和MEN β (neat12)长链非编码rna在细胞核中积累到高水平,它们分别在癌症进展和核副斑的形成中起关键作用。然而,MALAT1和MEN β在tRNA生物发生机制生成其成熟的3 '端时不会发生聚腺苷化。在poly(a) tail的位置,这些转录本由高度保守的三螺旋结构稳定。sno - lncrna同样缺乏poly(A)尾部,而是在其5 ‘和3 ’端具有snoRNA结构。最近的工作还发现了一些由前mrna剪接机制产生的丰富的环状rna,这些环状rna可以抵抗外切酶的降解。由于这些不同的转录物使用非规范策略来确保它们的稳定性,越来越清楚的是,长链非编码rna可能经常受到独特的转录后控制机制的调节。这篇文章是题为《长链非编码RNA分类学的线索》特刊的一部分。
Most of the human genome is transcribed, yielding a complex network of transcripts that includes tens of thousands of long noncoding RNAs. Many of these transcripts have a 5′ cap and a poly(A) tail, yet some of the most abundant long noncoding RNAs are processed in unexpected ways and lack these canonical structures. Here, I highlight the mechanisms by which several of these well-characterized noncoding RNAs are generated, stabilized, and function. The MALAT1 and MEN β (NEAT1_2) long noncoding RNAs each accumulate to high levels in the nucleus, where they play critical roles in cancer progression and the formation of nuclear paraspeckles, respectively. Nevertheless, MALAT1 and MEN β are not polyadenylated as the tRNA biogenesis machinery generates their mature 3′ ends. In place of a poly(A) tail, these transcripts are stabilized by highly conserved triple helical structures. Sno-lncRNAs likewise lack poly(A) tails and instead have snoRNA structures at their 5′ and 3′ ends. Recent work has additionally identified a number of abundant circular RNAs generated by the pre-mRNA splicing machinery that are resistant to degradation by exonucleases. As these various transcripts use non-canonical strategies to ensure their stability, it is becoming increasingly clear that long noncoding RNAs may often be regulated by unique post-transcriptional control mechanisms. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy.