Rational extension of the ribosome biogenesis pathway using network-guided genetics.
Rational extension of the ribosome biogenesis pathway using network-guided genetics.
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DOI：
10.1371/journal.pbio.1000213
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发表时间：
2009-10
期刊：
影响因子：
9.8
通讯作者：
Marcotte EM
中科院分区：
文献类型：
--
作者：
Li Z;Lee I;Moradi E;Hung NJ;Johnson AW;Marcotte EM
基因网络是将候选基因与生物过程联系起来的有效途径。在这里，网络被用来发现超过15个新的基因的核糖体亚基成熟，rRNA加工，核糖体从细胞核输出。核糖体的生物发生是在所有真核生物中保守的基本细胞过程，并且已知需要>170个基因用于核糖体组分通过多个细胞区室的组装、修饰和运输。尽管进行了深入的研究，但这一途径可能涉及许多其他基因。在这里，我们采用网络引导遗传学的方法，将候选基因与生物过程，利用功能基因组学和蛋白质组学研究的最新进展，以计算确定额外的核糖体生物合成基因。我们在一系列测定中实验评估了超过100个候选酵母基因，确认涉及至少15个新基因，包括之前未表征的基因（YDL 063 C、YIL 091 C、YOR 287 C、YOR 006 C/TSR 3、YOL 022 C/TSR 4）。我们将新基因与核糖体亚基成熟、核糖体颗粒结合和核糖体亚基核输出的特定方面相关联，并且我们鉴定了5S、7S、20 S、27 S和35 S rRNA加工所需的特定基因。这些结果揭示了核糖体生物发生和mRNA剪接之间的新联系，并为生物发生途径增加了>10%的新基因-大多数与人类直系同源物，显着扩展了我们对普遍保守的真核过程的理解。核糖体是负责构建新蛋白质的极其复杂的细胞机器。在真核细胞中，如酵母，每个核糖体含有80多种蛋白质或RNA成分。这些复杂的机器本身必须由一个甚至更复杂的机器组装起来，这个机器跨越多个细胞区室，在一系列有序的加工事件中涉及大约200个组件，导致成熟核糖体的两个半部分，即40 S和60 S组件，输送到细胞质。核糖体的生物发生机制只得到了部分表征，许多证据表明还有其他未知的成分。我们采用了一种称为网络引导遗传学的新兴计算技术来识别这一途径的新候选基因。然后，我们在一系列实验测定中测试了候选基因，以确定这些基因在核糖体的生物发生中可能发挥的作用。这种方法被证明是发现参与核糖体生物合成的新基因的有效途径，显著扩展了我们对普遍保守的真核生物过程的理解。
Gene networks are an efficient route for associating candidate genes with biological processes. Here, networks are used to discover more than 15 new genes for ribosomal subunit maturation, rRNA processing, and ribosomal export from the nucleus. Biogenesis of ribosomes is an essential cellular process conserved across all eukaryotes and is known to require >170 genes for the assembly, modification, and trafficking of ribosome components through multiple cellular compartments. Despite intensive study, this pathway likely involves many additional genes. Here, we employ network-guided genetics—an approach for associating candidate genes with biological processes that capitalizes on recent advances in functional genomic and proteomic studies—to computationally identify additional ribosomal biogenesis genes. We experimentally evaluated >100 candidate yeast genes in a battery of assays, confirming involvement of at least 15 new genes, including previously uncharacterized genes (YDL063C, YIL091C, YOR287C, YOR006C/TSR3, YOL022C/TSR4). We associate the new genes with specific aspects of ribosomal subunit maturation, ribosomal particle association, and ribosomal subunit nuclear export, and we identify genes specifically required for the processing of 5S, 7S, 20S, 27S, and 35S rRNAs. These results reveal new connections between ribosome biogenesis and mRNA splicing and add >10% new genes—most with human orthologs—to the biogenesis pathway, significantly extending our understanding of a universally conserved eukaryotic process. Ribosomes are the extremely complex cellular machines responsible for constructing new proteins. In eukaryotic cells, such as yeast, each ribosome contains more than 80 protein or RNA components. These complex machines must themselves be assembled by an even more complex machinery spanning multiple cellular compartments and involving perhaps 200 components in an ordered series of processing events, resulting in delivery of the two halves of the mature ribosome, the 40S and 60S components, to the cytoplasm. The ribosome biogenesis machinery has been only partially characterized, and many lines of evidence suggest that there are additional components that are still unknown. We employed an emerging computational technique called network-guided genetics to identify new candidate genes for this pathway. We then tested the candidates in a battery of experimental assays to determine what roles the genes might play in the biogenesis of ribosomes. This approach proved an efficient route to the discovery of new genes involved in ribosome biogenesis, significantly extending our understanding of a universally conserved eukaryotic process.
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影响因子：
16
作者：
Grandi, P;Rybin, V;Hurt, E
通讯作者：
Hurt, E
影响因子：
64.8
作者：
Gavin, AC;Aloy, P;Superti-Furga, G
通讯作者：
Superti-Furga, G
DOI：
10.1101/sqb.2001.66.403
发表时间：
2001-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
Asano, K;Phan, L;Hinnebusch, AG
通讯作者：
Hinnebusch, AG
影响因子：
11.4
作者：
Audhya, A;Emr, SD
通讯作者：
Emr, SD
影响因子：
64.8
作者：
Dragon, F;Gallagher, JEG;Baserga, SJ
通讯作者：
Baserga, SJ