On the normalization of RNA equilibrium free energy to the length of the sequence

On the normalization of RNA equilibrium free energy to the length of the sequence
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DOI:
10.1093/nar/gng049
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发表时间:
2003-05-01
影响因子:
14.9
通讯作者:
Kasif, S
Kasif, S
中科院分区:
生物学2区
文献类型:
--
作者:
Pervouchine, DD;Graber, JH;Kasif, S

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对于RNA二级结构的稳定性没有统一的定义。在这里,我们提出了一种基于平衡自由能与序列长度归一化的方法:如果平衡自由能与片段长度的比值大于某个阈值,则RNA片段被认为是稳定的。丢弃归一化平衡自由能小于阈值的段,使我们可以观察不同稳定水平下的二级结构。二级结构预测算法仅局限于高度稳定的结构,允许进行许多简化,使其在计算上易于处理大序列,并且在全基因组范围内优于大多数其他方法。该方法应用于秀丽隐杆线虫基因组,定位编码稳定二级结构的区域。特别是,先前报道的56个微rna中有36个定位于基因组的4%。在秀丽隐杆线虫的基因组序列中发现了一小部分长(大于或等于400 nt)稳定的反向重复序列。它们的分布非常不均匀,并向染色体的末端倾斜。该方法可用于转录终止信号、推测的微RNA和其他涉及稳定RNA二级结构的调控元件的全基因组检测。
There is no universal definition of stability for RNA secondary structures. Here we present an approach that is based on normalization of the equilibrium free energy to the length of the sequence: a segment of RNA is said to be stable if the ratio of the equilibrium free energy to the length of the segment is greater than a certain threshold value. Discarding the segments whose normalized equilibrium free energies are smaller than the threshold allows us to view the secondary structure at different levels of stability. Confined to only highly stable structures, the algorithm for secondary structure prediction admits a number of simplifications that make it computationally tractable for large sequences and advantageous over most other methods on a genome-wide scale. This method was applied to the Caenorhabditis elegans genome to localize the regions that encode stable secondary structures. In particular, 36 of 56 previously reported micro-RNAs were localized to 4% of the genome. A fraction of long (greater than or equal to400 nt) stable inverted repeats in the genomic sequence of C.elegans was found. Their distribution is very uneven, and skewed towards the ends of chromosomes. This method can be used for genome-wide detection of transcription termination signals, putative micro-RNAs, and other regulatory elements that involve stable RNA secondary structures.