Elavl1a regulates zebrafish erythropoiesis via posttranscriptional control of gata1

Blood. 2014 Feb 27;123(9):1384-92. doi: 10.1182/blood-2013-09-526962. Epub 2014 Jan 14.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Animals, Genetically Modified
  • Binding Sites / genetics
  • Cell Line, Tumor
  • ELAV Proteins / physiology*
  • Embryo, Nonmammalian
  • Erythropoiesis / genetics*
  • GATA1 Transcription Factor / genetics*
  • GATA1 Transcription Factor / metabolism
  • Gene Expression Regulation, Developmental
  • HEK293 Cells
  • Humans
  • Mice
  • RNA Processing, Post-Transcriptional / genetics*
  • Zebrafish / embryology*
  • Zebrafish / genetics*
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism

Substances

  • 3' Untranslated Regions
  • ELAV Proteins
  • GATA1 Transcription Factor
  • Zebrafish Proteins
  • gata1a protein, zebrafish