title: Elavl1a regulates zebrafish erythropoiesis via posttranscriptional control of gata1.
abstract: The RNA-binding protein Elavl1 (also known as HuR) regulates gene expression at the posttranscriptional level. Early embryonic lethality of the mouse knockout challenges investigation into hematopoietic functions for Elavl1. We identified 2 zebrafish elavl1 genes, designated elavl1a (the predominant isoform during embryogenesis) and elavl1b. Knockdown of Elavl1a using specific morpholinos resulted in a striking loss of primitive embryonic erythropoiesis. Transcript levels for early hematopoietic regulatory genes including lmo2 and scl are unaltered, but levels of gata1 transcripts, encoding a key erythroid transcription factor, are significantly reduced in elavl1a morphants. Other mesoderm markers are mostly unchanged by depletion of Elav1a. The 3'-untranslated region (UTR) of gata1 contains putative Elavl1a-binding sites that support robust expression levels when fused to a transfected luciferase reporter gene, and Elavl1a binds the gata1 3'-UTR sequences in a manner dependent on these sites. Moreover, expression of a transgenic reporter specifically in developing embryonic erythroid cells is enhanced by addition of the gata1 3'UTR with intact Elavl1-binding sites. Injection of gata1 messenger RNA partially rescues the erythropoiesis defect caused by Elavl1 knockdown. Our study reveals a posttranscriptional regulatory mechanism by which RNA-binding protein Elavl1a regulates embryonic erythropoiesis by maintaining appropriate levels of gata1 expression.
authors.affiliation: Center for Vascular Biology, Department of Pathology and Laboratory Medicine, and.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Yi-Chien
authors.initials: YC
authors.lastname: Lu
authors.forename: Kezhi
authors.initials: K
authors.lastname: Dai
authors.forename: Ingrid
authors.initials: I
authors.lastname: Torregroza
authors.forename: Timothy
authors.initials: T
authors.lastname: Hla
authors.forename: Todd
authors.initials: T
authors.lastname: Evans
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D051959:ELAV Proteins / Q000502:physiology*; D004625:Embryo, Nonmammalian; D004920:Erythropoiesis / Q000235:genetics*; D050982:GATA1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D051959:ELAV Proteins; D050982:GATA1 Transcription Factor; D029961:Zebrafish Proteins; C494691:gata1a protein, zebrafish