Genome-wide searching for pseudouridylation guide snoRNAs:: analysis of the Saccharomyces cerevisiae genome

Genome-wide searching for pseudouridylation guide snoRNAs:: analysis of the Saccharomyces cerevisiae genome
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DOI:
10.1093/nar/gkh768
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发表时间:
2004-08-01
影响因子:
14.9
通讯作者:
Lowe, TM
Lowe, TM
中科院分区:
生物学2区
文献类型:
--
作者:
Schattner, P;Decatur, WA;Lowe, TM

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真核生物中最大的小RNA家族之一是H/ACA小核仁RNA (snoRNAs),其中大多数引导RNA假尿嘧啶的形成。到目前为止,还没有一种有效的专门用于鉴定H/ACA snoRNA基因序列的计算方法。我们已经开发了snoGPS,一个用于计算筛选H/ACA指导snoRNAs的基因组序列的程序。该程序实现了一种确定性筛选算法,结合概率模型对候选基因进行评分。本文报道了对酿酒酵母芽殖的snoGPS检测结果。6个候选的snoRNAs被证实为新的RNA转录本,其中5个被证实是在核糖体RNA的特定位点上形成伪尿嘧啶的向导。我们还预测了snnas与酿酒酵母rRNA中已知的假尿嘧啶位点之间的14个新的碱基对,其中12个碱基对通过基因破坏和同源假尿嘧啶位点的缺失得到了验证。我们的发现包括首次预测和验证在两个以上位点引导伪尿嘧啶修饰的snorna。通过这项工作,s.s erevisiae rRNA中44种已知伪尿嘧啶修饰中的41种已与经过验证的snoRNA相关联,从而提供了对任何物种中指导伪尿嘧啶化的H/ACA snoRNA的最完整描述。
One of the largest families of small RNAs in eukaryotes is the H/ACA small nucleolar RNAs (snoRNAs), most of which guide RNA pseudouridine formation. So far, an effective computational method specifically for identifying H/ACA snoRNA gene sequences has not been established. We have developed snoGPS, a program for computationally screening genomic sequences for H/ACA guide snoRNAs. The program implements a deterministic screening algorithm combined with a probabilistic model to score gene candidates. We report here the results of testing snoGPS on the budding yeast Saccharomyces cerevisiae. Six candidate snoRNAs were verified as novel RNA transcripts, and five of these were verified as guides for pseudouridine formation at specific sites in ribosomal RNA. We also predicted 14 new base-pairings between snoRNAs and known pseudouridine sites in S.cerevisiae rRNA, 12 of which were verified by gene disruption and loss of the cognate pseudouridine site. Our findings include the first prediction and verification of snoRNAs that guide pseudouridine modification at more than two sites. With this work, 41 of the 44 known pseudouridine modifications in S.cerevisiae rRNA have been linked with a verified snoRNA, providing the most complete accounting of the H/ACA snoRNAs that guide pseudouridlylation in any species.