Vertebrate MicroRNA genes
Vertebrate MicroRNA genes
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DOI：
10.1126/science.1080372
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发表时间：
2003-03-07
期刊：
影响因子：
56.9
通讯作者：
Bartel, DP
中科院分区：
文献类型：
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作者：
Lim, LP;Glasner, ME;Bartel, DP
MicroRNA（miRNAs）是一类丰富的22个核苷酸（nt）的非编码RNA，已知其中一些在转录后水平控制其他基因的表达（1-4）。我们开发了一种计算机程序（MiR-scan）来识别miRNA基因（5），并将其应用于识别脊椎动物中的大多数miRNA基因。MiRscan依赖于以下观察结果：已知的miRNA来源于具有特征性特征的遗传学保守的茎环前体RNA。MiRscan通过沿着每个保守的茎环传递21-nt窗口来评估保守的茎环作为miRNA前体，为每个窗口分配对数似然分数，该分数测量其属性与前50个实验验证的C. elegans miRNAs与C.人和小鼠基因组的比对区域的折叠，随后与红鳍东方鲀基因组进行比较，鉴定了15，000个人基因组区段，其落在预测的蛋白质编码基因之外，预测形成茎环，并且在三种脊椎动物物种中至少是松散保守的（6）。MiR扫描评估显示了一组由188个人类基因座组成的高分基因座，使用自然截止分数10，由此时分布的下降定义（图1）。这一组包括已知人类miRNA基因座的参考组的109个成员中的81个，灵敏度为0.74。事实上，仅使用线虫miRNA开发和训练的程序也可以识别大多数脊椎动物miRNA，这表明miRNA及其前体的通用特征在不同动物中广泛保守，即使大多数miRNA的序列并不广泛保守。我们的分析可用于计算人类miRNA基因数量的上限。如果所有188个候选者都是真实的miRNA基因，并且这些代表了总miRNA基因的74%，那么不超过
MicroRNAs (miRNAs) are an abundant class of 22-nucleotide (nt) noncoding RNAs, some of which are known to control the expression of other genes at the posttranscriptional level (1–4). We developed a computational procedure (MiR-scan) to identify miRNA genes (5) and apply it here to identify most of the miRNA genes in vertebrates. MiRscan relies on the observation that the known miRNAs derive from phylogenetically conserved stem loop precursor RNAs with characteristic features. MiRscan evaluates conserved stem loops as miRNA precursors by passing a 21-nt window along each conserved stem loop, assigning a log-likelihood score to each window that measures how well its attributes resemble those of the first 50 experimentally verified C. elegans miRNAs with C. briggsae homologs (2, 3, 5).Folding of aligned regions of the human and mouse genomes, with subsequent comparison to the pufferfish Fugu rubripes genome, identified 15,000 human genomic segments that fell out-side of predicted protein coding genes, were predicted to form stem loops, and were at least loosely conserved among the three vertebrate species (6). MiR-scan evaluation revealed a high-scoring set of 188 human loci, using a natural cutoff score of 10, defined by a dip in the distribution at this point (Fig. 1). This set included 81 of the 109 members of a reference set of known human miRNA loci, for a sensitivity of 0.74. The fact that a procedure developed and trained solely using nematode miRNAs could also identify most of the vertebrate miRNAs shows that the generic features of the miRNAs and their precursors are conserved broadly among diverse animals, even though the sequences of most miRNAs are not as broadly conserved. Our analysis can be used to calculate an upper bound on the number of human miRNA genes. If all 188 candidates were authentic miRNA genes and these represented 74% of the total miRNA genes, then there are no more than