Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells.
Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells.
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DOI：
10.1038/nature13802
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发表时间：
2014-11-06
期刊：
影响因子：
64.8
通讯作者：
Gilbert, Wendy V.
中科院分区：
文献类型：
--
作者：
Carlile, Thomas M.;Rojas-Duran, Maria F.;Zinshteyn, Boris;Shin, Hakyung;Bartoli, Kristen M.;Gilbert, Wendy V.
RNA 核苷的转录后修饰发生在所有生物体中。伪尿苷是非编码RNA中最丰富的修饰核苷，通过稳定RNA结构来增强转移RNA和核糖体RNA的功能。目前尚不清楚 mRNA 是否含有假尿苷，但人工假尿苷化会极大地影响 mRNA 功能——它通过促进核糖体解码中心的非规范碱基配对来改变遗传密码。然而，由于没有自然发生的 mRNA 假尿苷化的证据，其生理学尚不清楚。在这里，我们使用 Pseudo-seq 对酵母和人类 RNA 中的假尿苷化进行了全面分析，Pseudo-seq 是一种用于假尿苷鉴定的全基因组单核苷酸分辨率方法。伪序列准确识别非编码 RNA 中已知的修饰位点以及 100 个新位点，并揭示 mRNA 中的数百个假尿苷化位点。遗传分析使我们能够将大部分新修饰位点分配给七个保守的假尿苷合酶之一：Pus1-4、6、7 和 9。值得注意的是，mRNA 中的大多数假尿苷都是根据环境信号进行调节的，例如酵母中的营养缺乏和人类细胞中的血清饥饿。这些结果表明了一种通过诱导性 mRNA 修饰快速、受调控地重新布线遗传密码的机制。我们的研究结果揭示了假尿苷化的意想不到的作用，并为识别与人类疾病有关的假尿苷合酶的靶标提供了资源。
Post-transcriptional modification of RNA nucleosides occurs in all living organisms. Pseudouridine, the most abundant modified nucleoside in non-coding RNAs, enhances the function of transfer RNA and ribosomal RNA by stabilizing RNA structure. mRNAs were not known to contain pseudouridine, but artificial pseudouridylation dramatically affects mRNA function – it changes the genetic code by facilitating non-canonical base pairing in the ribosome decoding center. However, without evidence of naturally occurring mRNA pseudouridylation, its physiological was unclear. Here we present a comprehensive analysis of pseudouridylation in yeast and human RNAs using Pseudo-seq, a genome-wide, single-nucleotide-resolution method for pseudouridine identification. Pseudo-seq accurately identifies known modification sites as well as 100 novel sites in non-coding RNAs, and reveals hundreds of pseudouridylated sites in mRNAs. Genetic analysis allowed us to assign most of the new modification sites to one of seven conserved pseudouridine synthases, Pus1–4, 6, 7 and 9. Notably, the majority of pseudouridines in mRNA are regulated in response to environmental signals, such as nutrient deprivation in yeast and serum starvation in human cells. These results suggest a mechanism for the rapid and regulated rewiring of the genetic code through inducible mRNA modifications. Our findings reveal unanticipated roles for pseudouridylation and provide a resource for identifying the targets of pseudouridine synthases implicated in human disease.
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影响因子：
64.8
作者：
Fernandez, Israel S.;Chyan Leong Ng;Kelley, Ann C.;Wu, Guowei;Yu, Yi-Tao;Ramakrishnan, V.
通讯作者：
Ramakrishnan, V.
DOI：
10.1093/bioinformatics/btp250
发表时间：
2009-08-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Darty K;Denise A;Ponty Y
通讯作者：
Ponty Y
影响因子：
9.8
作者：
Bykhovskaya, Y;Casas, K;Fischel-Ghodsian, N
通讯作者：
Fischel-Ghodsian, N
影响因子：
14.9
作者：
Jühling F;Mörl M;Hartmann RK;Sprinzl M;Stadler PF;Pütz J
通讯作者：
Pütz J
影响因子：
2.9
作者：
HALL, KB;MCLAUGHLIN, LW
通讯作者：
MCLAUGHLIN, LW