CAP1, a target of miR-144/451, negatively regulates erythroid differentiation and enucleation

J Cell Mol Med. 2021 Mar;25(5):2377-2389. doi: 10.1111/jcmm.16067. Epub 2021 Jan 26.

Abstract

The exact molecular mechanism underlying erythroblast enucleation has been a fundamental biological question for decades. In this study, we found that miR-144/451 critically regulated erythroid differentiation and enucleation. We further identified CAP1, a G-actin-binding protein, as a direct target of miR-144/451 in these processes. During terminal erythropoiesis, CAP1 expression declines along with gradually increased miR-144/451 levels. Enforced CAP1 up-regulation inhibits the formation of contractile actin rings in erythroblasts and prevents their terminal differentiation and enucleation. Our findings reveal a negative regulatory role of CAP1 in miR-144/451-mediated erythropoiesis and thus shed light on how microRNAs fine-tune terminal erythroid development through regulating actin dynamics.

Keywords: miR-144/451; CAP1; actin filament remodelling; enucleation; erythropoiesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Biomarkers
  • Cell Differentiation / genetics*
  • Cell Line
  • Cells, Cultured
  • Erythroid Precursor Cells / cytology
  • Erythroid Precursor Cells / metabolism*
  • Erythropoiesis / genetics
  • Gene Expression Regulation, Developmental*
  • Immunophenotyping
  • Mice
  • MicroRNAs / genetics*
  • RNA Interference*
  • Serine Endopeptidases / genetics*

Substances

  • 3' Untranslated Regions
  • Biomarkers
  • MIRN144 microRNA, mouse
  • MicroRNAs
  • Mirn451 microRNA, mouse
  • Serine Endopeptidases
  • prostasin