Hartman Institute for Therapeutic Organ Regeneration

Elavl1a regulates zebrafish erythropoiesis via posttranscriptional control of gata1.

TitleElavl1a regulates zebrafish erythropoiesis via posttranscriptional control of gata1.
Publication TypeJournal Article
Year of Publication2014
AuthorsLi X, Lu Y-C, Dai K, Torregroza I, Hla T, Evans T
JournalBlood
Volume123
Issue9
Pagination1384-92
Date Published2014 Feb 27
ISSN1528-0020
Keywords3' Untranslated Regions, Animals, Animals, Genetically Modified, Binding Sites, Cell Line, Tumor, ELAV Proteins, Embryo, Nonmammalian, Erythropoiesis, GATA1 Transcription Factor, Gene Expression Regulation, Developmental, HEK293 Cells, Humans, Mice, RNA Processing, Post-Transcriptional, Zebrafish, Zebrafish Proteins
Abstract

<p>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.</p>

DOI10.1182/blood-2013-09-526962
Alternate JournalBlood
PubMed ID24425803
PubMed Central IDPMC3938149
Grant ListHL49094 / HL / NHLBI NIH HHS / United States
R01 HL049094 / HL / NHLBI NIH HHS / United States
HL56182 / HL / NHLBI NIH HHS / United States
R01 HL056182 / HL / NHLBI NIH HHS / United States
R37 HL056182 / HL / NHLBI NIH HHS / United States

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Hartman Institute for Therapeutic Organ Regeneration
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