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英国诺里奇研究园Yiliang Ding、Caroline Dean等研究人员合作利用体内单分子分析揭示COOLAIR RNA结构的多样性。相关论文于2022年8月17日在线发表在《自然》杂志上。

研究人员表示，细胞RNA在其可变加工和二级结构方面是异质的，但对这种复杂性的功能重要性仍知之甚少。一组经过可变加工的反义非编码转录物，统称为COOLAIR，产生于拟南芥的开花抑制基因座FLOWERING LOCUS C（FLC）。COOLAIR的不同亚型影响FLC在温暖和寒冷条件下的转录输出。

为了进一步研究COOLAIR的功能，研究人员开发了一种RNA结构分析方法，以确定单个RNA分子的体内结构，而不是RNA群体的平均值。结果表明，COOLAIR转录本的单个亚型采用了具有不同构象动态的多种结构。在温暖条件下，主要的远端多腺苷酸化的COOLAIR亚型采用三种主要的结构构象，其比例和构象在冷暴露后发生变化。与近端多腺苷酸化的COOLAIR相比，一个可变剪接的、强冷上调的远端COOLAIR亚型显示出高结构多样性。

一个高度变化的COOLAIR结构元件被确定为与FLC转录起始位点互补。影响该区域结构的突变改变了FLC的表达和开花时间，这与COOLAIR结构在FLC转录中的重要调节作用一致。这项工作表明，非编码RNA转录本的亚型采用了多种不同的、与功能相关的结构构象，这些构象的丰度和形状随外界条件的变化而变化。

附：英文原文

Title: In vivo single-molecule analysis reveals COOLAIR RNA structural diversity

Author: Yang, Minglei, Zhu, Pan, Cheema, Jitender, Bloomer, Rebecca, Mikulski, Pawel, Liu, Qi, Zhang, Yueying, Dean, Caroline, Ding, Yiliang

Issue&Volume: 2022-08-17

Abstract: Cellular RNAs are heterogeneous with respect to their alternative processing and secondary structures, but the functional importance of this complexity is still poorly understood. A set of alternatively processed antisense non-coding transcripts, which are collectively called COOLAIR, are generated at the Arabidopsis floral-repressor locus FLOWERING LOCUS C (FLC)1. Different isoforms of COOLAIR influence FLC transcriptional output in warm and cold conditions2,3,4,5,6,7. Here, to further investigate the function of COOLAIR, we developed an RNA structure-profiling method to determine the in vivo structure of single RNA molecules rather than the RNA population average. This revealed that individual isoforms of the COOLAIR transcript adopt multiple structures with different conformational dynamics. The major distally polyadenylated COOLAIR isoform in warm conditions adopts three predominant structural conformations, the proportions and conformations of which change after cold exposure. An alternatively spliced, strongly cold-upregulated distal COOLAIR isoform6 shows high structural diversity, in contrast to proximally polyadenylated COOLAIR. A hyper-variable COOLAIR structural element was identified that was complementary to the FLC transcription start site. Mutations altering the structure of this region changed FLC expression and flowering time, consistent with an important regulatory role of the COOLAIR structure in FLC transcription. Our work demonstrates that isoforms of non-coding RNA transcripts adopt multiple distinct and functionally relevant structural conformations, which change in abundance and shape in response to external conditions.

DOI: 10.1038/s41586-022-05135-9

Source: https://www.nature.com/articles/s41586-022-05135-9

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