Correlation between sequence conservation and structural thermodynamics of microRNA precursors from human, mouse, and chicken genomes

Correlation between sequence conservation and structural thermodynamics of microRNA precursors from human, mouse, and chicken genomes
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人类、小鼠和鸡基因组中 microRNA 前体的序列保守性与结构热力学之间的相关性

DOI:
10.1186/1471-2148-10-329
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发表时间:
2010-10-27
影响因子:
3.4
通讯作者:
Li, Songgang
Li, Songgang
中科院分区:
生物学2区
文献类型:
--
作者:
Ni, Ming;Shu, Wenjie;Li, Songgang

文献摘要

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背景研究表明microRNA前体(pre-miRNAs)具有比其他天然RNA(tRNA、rRNA和mRNA)和人工RNA序列更稳定的二级结构。然而,具有超稳定二级结构的pre-miRNA尚未被研究。目前尚不清楚前体miRNA序列是否倾向于或反对超稳定结构?此外,前体miRNA的结构热力学稳定性和它们的evolution.ResultsWe之间的关系仍然不清楚,我们研究了前体miRNA序列保守性和结构稳定性之间的相关性,通过调整最小折叠自由能在前体miRNA分离自人类,小鼠和鸡。分析表明,保守和非保守的pre-miRNA序列具有相似的平均稳定性的结构。然而,相对超稳定和不稳定的pre-miRNAs比具有中等稳定性的pre-miRNAs更可能是非保守的。非保守的pre-miRNAs含有比A+U更多的G+C核苷酸,而保守的pre-miRNAs含有更多的A+U核苷酸。值得注意的是,保守的pre-miRNAs的U含量特别高于非保守的pre-miRNAs。进一步的调查表明,保守和非保守的前体miRNA表现出不同的结构元素的功能,即使他们有可比水平的stability.ConclusionsWe提出,有一个结构热力学稳定性和序列保守的前体miRNA从人类,小鼠和鸡的基因组之间的相关性。我们的分析表明,具有相对超稳定或不稳定结构的pre-miRNAs比具有中等稳定结构的pre-miRNAs更不受自然选择的青睐。比较非保守和保守的pre-miRNA的核苷酸组成表明U核苷酸在pre-miRNA进化过程中的重要性。在保守的pre-miRNAs中也检测到几个特征性的结构元件。
BackgroundPrevious studies have shown that microRNA precursors (pre-miRNAs) have considerably more stable secondary structures than other native RNAs (tRNA, rRNA, and mRNA) and artificial RNA sequences. However, pre-miRNAs with ultra stable secondary structures have not been investigated. It is not known if there is a tendency in pre-miRNA sequences towards or against ultra stable structures? Furthermore, the relationship between the structural thermodynamic stability of pre-miRNA and their evolution remains unclear.ResultsWe investigated the correlation between pre-miRNA sequence conservation and structural stability as measured by adjusted minimum folding free energies in pre-miRNAs isolated from human, mouse, and chicken. The analysis revealed that conserved and non-conserved pre-miRNA sequences had structures with similar average stabilities. However, the relatively ultra stable and unstable pre-miRNAs were more likely to be non-conserved than pre-miRNAs with moderate stability. Non-conserved pre-miRNAs had more G+C than A+U nucleotides, while conserved pre-miRNAs contained more A+U nucleotides. Notably, the U content of conserved pre-miRNAs was especially higher than that of non-conserved pre-miRNAs. Further investigations showed that conserved and non-conserved pre-miRNAs exhibited different structural element features, even though they had comparable levels of stability.ConclusionsWe proposed that there is a correlation between structural thermodynamic stability and sequence conservation for pre-miRNAs from human, mouse, and chicken genomes. Our analyses suggested that pre-miRNAs with relatively ultra stable or unstable structures were less favoured by natural selection than those with moderately stable structures. Comparison of nucleotide compositions between non-conserved and conserved pre-miRNAs indicated the importance of U nucleotides in the pre-miRNA evolutionary process. Several characteristic structural elements were also detected in conserved pre-miRNAs.