title: Ribosomal Proteins Rpl22 and Rpl22l1 Control Morphogenesis by Regulating Pre-mRNA Splicing.
abstract: 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.
authors.affiliation: Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors.forename: Monique N
authors.initials: MN
authors.lastname: O'Leary
authors.affiliation: Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Suraj
authors.initials: S
authors.lastname: Peri
authors.affiliation: Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Minshi
authors.initials: M
authors.lastname: Wang
authors.affiliation: Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Jikun
authors.initials: J
authors.lastname: Zha
authors.affiliation: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Melov
authors.affiliation: Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Dietmar J
authors.initials: DJ
authors.lastname: Kappes
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rhodes
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Amieux
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Morris
authors.affiliation: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kennedy
authors.affiliation: Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Electronic address: david.wiest@fccc.edu.
authors.forename: David L
authors.initials: DL
authors.lastname: Wiest
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005091:Exons / Q000235:genetics; D054262:Gastrulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009024:Morphogenesis / Q000235:genetics; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D051899:Smad2 Protein / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C522051:RPL22 protein, mouse; C000608557:RPL22L1 protein, mouse; D012269:Ribosomal Proteins; C000624805:Rpl22 protein, zebrafish; C000624806:Rpl22l1 protein, zebrafish; D051899:Smad2 Protein; D029961:Zebrafish Proteins
keywords: Rpl22; Rpl22l1; Smad2; extraribosomal function; gastrulation; hnRNP-A1; morphogenesis; paralog; pre-mRNA splicing; ribosomal protein