PUBLICATION
Elavl1a regulates zebrafish erythropoiesis via posttranscriptional control of gata1
- Authors
- Li, X., Lu, Y.C., Dai, K., Torregroza, I., Hla, T., Evans, T.
- ID
- ZDB-PUB-220929-39
- Date
- 2014
- Source
- Blood 123: 1384-92 (Journal)
- Registered Authors
- Evans, Todd, Li, Xi
- Keywords
- none
- MeSH Terms
-
- Humans
- ELAV Proteins/physiology*
- HEK293 Cells
- Gene Expression Regulation, Developmental
- Animals, Genetically Modified
- RNA Processing, Post-Transcriptional/genetics*
- Zebrafish/embryology*
- Zebrafish/genetics*
- GATA1 Transcription Factor/genetics*
- GATA1 Transcription Factor/metabolism
- Cell Line, Tumor
- Embryo, Nonmammalian
- Mice
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- Binding Sites/genetics
- Erythropoiesis/genetics*
- 3' Untranslated Regions/genetics
- Animals
- PubMed
- 24425803 Full text @ Blood
Citation
Li, X., Lu, Y.C., Dai, K., Torregroza, I., Hla, T., Evans, T. (2014) Elavl1a regulates zebrafish erythropoiesis via posttranscriptional control of gata1. Blood. 123:1384-92.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping