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具有功能性瞬态结构的四个RNA家族。

Four RNA families with functional transient structures.

作者信息

Zhu Jing Yun A, Meyer Irmtraud M

机构信息

a Centre for High-Throughput Biology and Department of Computer Science and Department of Medical Genetics; University of British Columbia ; Vancouver , BC , Canada.

出版信息

RNA Biol. 2015;12(1):5-20. doi: 10.1080/15476286.2015.1008373.

Abstract

Protein-coding and non-coding RNA transcripts perform a wide variety of cellular functions in diverse organisms. Several of their functional roles are expressed and modulated via RNA structure. A given transcript, however, can have more than a single functional RNA structure throughout its life, a fact which has been previously overlooked. Transient RNA structures, for example, are only present during specific time intervals and cellular conditions. We here introduce four RNA families with transient RNA structures that play distinct and diverse functional roles. Moreover, we show that these transient RNA structures are structurally well-defined and evolutionarily conserved. Since Rfam annotates one structure for each family, there is either no annotation for these transient structures or no such family. Thus, our alignments either significantly update and extend the existing Rfam families or introduce a new RNA family to Rfam. For each of the four RNA families, we compile a multiple-sequence alignment based on experimentally verified transient and dominant (dominant in terms of either the thermodynamic stability and/or attention received so far) RNA secondary structures using a combination of automated search via covariance model and manual curation. The first alignment is the Trp operon leader which regulates the operon transcription in response to tryptophan abundance through alternative structures. The second alignment is the HDV ribozyme which we extend to the 5' flanking sequence. This flanking sequence is involved in the regulation of the transcript's self-cleavage activity. The third alignment is the 5' UTR of the maturation protein from Levivirus which contains a transient structure that temporarily postpones the formation of the final inhibitory structure to allow translation of maturation protein. The fourth and last alignment is the SAM riboswitch which regulates the downstream gene expression by assuming alternative structures upon binding of SAM. All transient and dominant structures are mapped to our new alignments introduced here.

摘要

蛋白质编码和非编码RNA转录本在不同生物体中执行多种细胞功能。它们的一些功能作用是通过RNA结构来表达和调节的。然而,一个给定的转录本在其整个生命周期中可能具有不止一种功能性RNA结构,这一事实此前一直被忽视。例如,瞬时RNA结构仅在特定的时间间隔和细胞条件下存在。我们在此介绍四个具有瞬时RNA结构的RNA家族,它们发挥着独特而多样的功能作用。此外,我们表明这些瞬时RNA结构在结构上定义明确且在进化上保守。由于Rfam为每个家族注释一种结构,因此对于这些瞬时结构要么没有注释,要么不存在这样的家族。因此,我们的比对要么显著更新和扩展现有的Rfam家族,要么向Rfam引入一个新的RNA家族。对于这四个RNA家族中的每一个,我们基于实验验证的瞬时和显性(在热力学稳定性和/或迄今为止受到的关注方面占主导)RNA二级结构,通过协方差模型自动搜索和人工编辑相结合的方式编制了一个多序列比对。第一个比对是色氨酸操纵子前导序列,它通过替代结构响应色氨酸丰度来调节操纵子转录。第二个比对是丁型肝炎病毒核酶,我们将其扩展到5'侧翼序列。该侧翼序列参与转录本自我切割活性的调节。第三个比对是来自微小噬菌体的成熟蛋白的5'非翻译区,它包含一个瞬时结构,该结构暂时推迟最终抑制结构的形成,以允许成熟蛋白的翻译。第四个也是最后一个比对是SAM核糖开关,它通过在结合SAM时呈现替代结构来调节下游基因表达。所有瞬时和显性结构都映射到我们在此引入的新比对中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e5d/4615214/7db34edb114b/krnb-12-01-1008373-g001.jpg

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