Zhang Yong, O'Leary Monique N, Peri Suraj, Wang Minshi, Zha Jikun, Melov Simon, Kappes Dietmar J, Feng Qing, Rhodes Jennifer, Amieux Paul S, Morris David R, Kennedy Brian K, Wiest David L
Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Buck Institute for Research on Aging, Novato, CA 94945, USA.
Cell Rep. 2017 Jan 10;18(2):545-556. doi: 10.1016/j.celrep.2016.12.034.
Most ribosomal proteins (RP) are regarded as essential, static components that contribute only 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.
大多数核糖体蛋白（RP）被视为必不可少的静态成分，仅对核糖体生物合成和蛋白质合成起作用。然而，新出现的证据表明，RNA结合型RP是动态的，可通过执行“核糖体之外的”调节功能来影响细胞过程，这些功能包括与特定关键靶mRNA结合。我们在此报告，RP中的Rpl22及其高度同源的旁系同源物Rpl22-Like1（Rpl22l1或Like1）在胚胎发生中发挥关键的核糖体之外的作用。实际上，它们通过在发育过程中受调控地定位于细胞核来拮抗控制形态发生，在细胞核中它们调节编码smad2的前体mRNA的剪接，smad2是Nodal/TGF-β信号传导的重要转录效应因子。在原肠胚形成过程中，Rpl22与smad2前体mRNA的内含子序列结合，并与hnRNP-A1协同诱导外显子9跳跃。其旁系同源物Like1则相反，它促进外显子9包含在成熟转录本中。这些RP在控制形态发生中的核作用代表了RP一种根本不同且范式转变的作用模式。
