Frac-seq reveals isoform-specific recruitment to polyribosomes.
Frac-seq reveals isoform-specific recruitment to polyribosomes.
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DOI：
10.1101/gr.148585.112
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发表时间：
2013-10
期刊：
影响因子：
7
通讯作者：
Sanford JR
中科院分区：
文献类型：
--
作者：
Sterne-Weiler T;Martinez-Nunez RT;Howard JM;Cvitovik I;Katzman S;Tariq MA;Pourmand N;Sanford JR
几乎所有人类蛋白质编码基因的准确表达都需要前mRNA剪接。然而，剪接也在协调后续的前mRNA加工步骤中发挥重要作用，如多聚腺苷化和mRNA输出。在这里，我们测试了这样的假设，即核前信使核糖核酸处理影响替代信使核糖体异构体的多核糖体关联。通过比较胞浆和多聚核糖体提取物中的异构体比率，我们确定了30%(597/1954年)的∼加工事件的替代产物在这些亚细胞组分之间有差异地分配。许多呈现异构体特异性多核糖体结合的事件在哺乳动物基因组中高度保守，这突显了它们可能的生物学重要性。我们发现，多聚核糖体结合的差异可以解释，至少部分原因是观察到选择性剪接改变了mRNAs异构体的顺式调控格局。例如，5‘非编码区上游开放阅读框(UORF)的包含或排除以及3’非编码区中的Alu元件和microRNA靶点对替代mRNA亚型的多核糖体结合有很大影响。综上所述，我们的数据首次证明了选择性剪接和所产生的mRNA亚型的翻译控制之间的潜在联系。
Pre-mRNA splicing is required for the accurate expression of virtually all human protein coding genes. However, splicing also plays important roles in coordinating subsequent steps of pre-mRNA processing such as polyadenylation and mRNA export. Here, we test the hypothesis that nuclear pre-mRNA processing influences the polyribosome association of alternative mRNA isoforms. By comparing isoform ratios in cytoplasmic and polyribosomal extracts, we determined that the alternative products of ∼30% (597/1954) of mRNA processing events are differentially partitioned between these subcellular fractions. Many of the events exhibiting isoform-specific polyribosome association are highly conserved across mammalian genomes, underscoring their possible biological importance. We find that differences in polyribosome association may be explained, at least in part by the observation that alternative splicing alters the cis-regulatory landscape of mRNAs isoforms. For example, inclusion or exclusion of upstream open reading frames (uORFs) in the 5′UTR as well as Alu-elements and microRNA target sites in the 3′UTR have a strong influence on polyribosome association of alternative mRNA isoforms. Taken together, our data demonstrate for the first time the potential link between alternative splicing and translational control of the resultant mRNA isoforms.
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影响因子：
7
作者：
Hausser J;Syed AP;Bilen B;Zavolan M
通讯作者：
Zavolan M
影响因子：
48
作者：
Katz, Yarden;Wang, Eric T.;Airoldi, Edoardo M.;Burge, Christopher B.
通讯作者：
Burge, Christopher B.
影响因子：
14.9
作者：
Grillo G;Turi A;Licciulli F;Mignone F;Liuni S;Banfi S;Gennarino VA;Horner DS;Pavesi G;Picardi E;Pesole G
通讯作者：
Pesole G
影响因子：
64.8
作者：
Hachet, O;Ephrussi, A
通讯作者：
Ephrussi, A
影响因子：
14.9
作者：
Lin, XK;Parsels, LA;Chu, E
通讯作者：
Chu, E