title: Control of hematopoietic stem cell emergence by antagonistic functions of ribosomal protein paralogs.
abstract: It remains controversial whether the highly homologous ribosomal protein (RP) paralogs found in lower eukaryotes have distinct functions and this has not been explored in vertebrates. Here we demonstrate that despite ubiquitous expression, the RP paralogs, Rpl22 and Rpl22-like1 (Rpl22l1) play essential, distinct, and antagonistic roles in hematopoietic development. Knockdown of Rpl22 in zebrafish embryos selectively blocks the development of T lineage progenitors after they have seeded the thymus. In contrast, knockdown of the Rpl22 paralog, Rpl22l1, impairs the emergence of hematopoietic stem cells (HSC) in the aorta-gonad-mesonephros by abrogating Smad1 expression and the consequent induction of essential transcriptional regulator, Runx1. Indeed, despite the ability of both paralogs to bind smad1 RNA, Rpl22 and Rpl22l1 have opposing effects on Smad1 expression. Accordingly, circumstances that tip the balance of these paralogs in favor of Rpl22 (e.g., Rpl22l1 knockdown or Rpl22 overexpression) result in repression of Smad1 and blockade of HSC emergence.
authors: Blood Cell Development and Cancer Keystone, Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors: Yong
authors: Y
authors: Zhang
authors: Anne-Cécile E
authors: AC
authors: Duc
authors: Shuyun
authors: S
authors: Rao
authors: Xiao-Li
authors: XL
authors: Sun
authors: Alison N
authors: AN
authors: Bilbee
authors: Michele
authors: M
authors: Rhodes
authors: Qin
authors: Q
authors: Li
authors: Dietmar J
authors: DJ
authors: Kappes
authors: Jennifer
authors: J
authors: Rhodes
authors: David L
authors: DL
authors: Wiest
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D019070:Cell Lineage; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D051898:Smad1 Protein / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D012333:RNA, Messenger; D012269:Ribosomal Proteins; D051898:Smad1 Protein; D029961:Zebrafish Proteins