Ribosomal Proteins Rpl22 and Rpl22l1 Control Morphogenesis by Regulating Pre-mRNA Splicing.
Ribosomal Proteins Rpl22 and Rpl22l1 Control Morphogenesis by Regulating Pre-mRNA Splicing.
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DOI：
10.1016/j.celrep.2016.12.034
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发表时间：
2017-01-10
期刊：
影响因子：
8.8
通讯作者：
Wiest DL
中科院分区：
文献类型：
--
作者：
Zhang Y;O'Leary MN;Peri S;Wang M;Zha J;Melov S;Kappes DJ;Feng Q;Rhodes J;Amieux PS;Morris DR;Kennedy BK;Wiest DL
大多数核糖体蛋白（RP）被认为是必不可少的静态成分，仅有助于核糖体生物发生和蛋白质合成。选择，关键目标mRNA。或类似1），在胚胎发生中起关键的外虫外作用。在Gastulation期间，RPL22与SMAD2前MRNA的内含子序列结合，并与HNRNP-A1合作诱导外显子9与其旁系同源物相反，它促进了外显子9在成熟的转录中的包含。
Zhang等人表明，核糖体蛋白可以在与核糖体分离时执行基本重要性的调节功能。与HnRNPA1合作的SMAD2 Pre-mRNA。
Most ribosomal proteins (RP) are regarded as essential, static components that only contribute to ribosome biogenesis and protein synthesis. However, emerging evidence suggests that RNA-binding RP are dynamic and can influence cellular processes by performing “extraribosomal”, regulatory functions involving binding to select, critical target mRNAs. We report here that the RP, Rpl22, and its highly homologous paralog, Rpl22-Like1 (Rpl22l1 or Like1), play critical, extraribosomal roles in embryogenesis. Indeed, they antagonistically control morphogenesis through developmentally-regulated localization to the nucleus where they modulate splicing of the pre-mRNA encoding smad2, an essential transcriptional effector of Nodal/TGF-β signaling. During gastrulation, Rpl22 binds to intronic sequences of smad2 pre-mRNA and induces exon 9 skipping in cooperation with hnRNP-A1. This action is opposed by its paralog, Like1, which promotes exon 9 inclusion in the mature transcript. The nuclear roles of these RP in controlling morphogenesis represent a fundamentally different and paradigm-shifting mode of action for RP. Zhang et al., reveal that ribosomal proteins can perform regulatory functions of fundamental importance while separated from the ribosome. They demonstrate that ribosomal proteins Rpl22 and Rpl22-Like1 (Like1) are retained in the nucleus during gastrulation where they control morphogenesis by modulating the splicing of Smad2 pre-mRNA in cooperation with HNRNPA1.