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ZFIN ID: ZDB-PUB-171204-53
Ribosomal Proteins Rpl22 and Rpl22l1 Control Morphogenesis by Regulating Pre-mRNA Splicing
Zhang, Y., O'Leary, M.N., Peri, S., Wang, M., Zha, J., Melov, S., Kappes, D.J., Feng, Q., Rhodes, J., Amieux, P.S., Morris, D.R., Kennedy, B.K., Wiest, D.L.
Date: 2017
Source: Cell Reports 18: 545-556 (Journal)
Registered Authors: Rhodes, Jennifer
Keywords: Rpl22, Rpl22l1, Smad2, extraribosomal function, gastrulation, hnRNP-A1, morphogenesis, paralog, pre-mRNA splicing, ribosomal protein
MeSH Terms:
  • Animals
  • Embryo, Mammalian/metabolism
  • Embryo, Nonmammalian/metabolism
  • Exons/genetics
  • Gastrulation/genetics
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Heterogeneous Nuclear Ribonucleoprotein A1/metabolism
  • Mice, Inbred C57BL
  • Morphogenesis*/genetics
  • RNA Precursors/genetics*
  • RNA Precursors/metabolism
  • RNA Splicing/genetics*
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • RNA-Binding Proteins/genetics
  • RNA-Binding Proteins/metabolism*
  • Ribosomal Proteins/genetics
  • Ribosomal Proteins/metabolism*
  • Smad2 Protein/metabolism
  • Subcellular Fractions/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 28076796 Full text @ Cell Rep.
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.