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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
Ribosomal Proteins Rpl22 and Rpl22l1 Control Morphogenesis by Regulating Pre-mRNA Splicing
Cell Rep. 2017 Jan 10;18(2) :545-556
PMID: 28076796    PMCID: PMC5234864    URL: https://www.ncbi.nlm.nih.gov/pubmed/28076796
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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-beta 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.
2211-1247 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 R56 AI110985/AI/NIAID NIH HHS/United States P50 CA100632/CA/NCI NIH HHS/United States R01 AI110985/AI/NIAID NIH HHS/United States P30 CA006927/CA/NCI NIH HHS/United States T32 CA009035/CA/NCI NIH HHS/United States Journal Article United States Cell Rep. 2017 Jan 10;18(2):545-556. doi: 10.1016/j.celrep.2016.12.034.