Title | Elavl1a regulates zebrafish erythropoiesis via posttranscriptional control of gata1. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Li X, Lu Y-C, Dai K, Torregroza I, Hla T, Evans T |
Journal | Blood |
Volume | 123 |
Issue | 9 |
Pagination | 1384-92 |
Date Published | 2014 Feb 27 |
ISSN | 1528-0020 |
Keywords | 3' 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> |
DOI | 10.1182/blood-2013-09-526962 |
Alternate Journal | Blood |
PubMed ID | 24425803 |
PubMed Central ID | PMC3938149 |
Grant List | HL49094 / 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 |