PUBLICATION

A non-canonical function of telomerase RNA in the regulation of developmental myelopoiesis in zebrafish

Authors
Alcaraz-Pérez, F., García-Castillo, J., García-Moreno, D., López-Muñoz, A., Anchelin, M., Angosto, D., Zon, L.I., Mulero, V., and Cayuela, M.L.
ID
ZDB-PUB-140410-20
Date
2014
Source
Nature communications   5: 3228 (Journal)
Registered Authors
Mulero, Victor, Zon, Leonard I.
Keywords
Disease genetics, Molecular biology, Myelopoiesis
MeSH Terms
  • Animals
  • Blood Cells/metabolism
  • Embryo, Nonmammalian/enzymology*
  • GATA1 Transcription Factor/metabolism
  • Hematopoietic Stem Cells
  • Myelopoiesis*
  • Neutropenia
  • Proto-Oncogene Proteins/metabolism
  • RNA/metabolism*
  • Telomerase/metabolism*
  • Trans-Activators/metabolism
  • Zebrafish
  • Zebrafish Proteins/metabolism
PubMed
24496182 Full text @ Nat. Commun.
Abstract

Dyskeratosis congenita (DC) is an inherited disorder with mutations affecting telomerase or telomeric proteins. DC patients usually die of bone marrow failure. Here we show that genetic depletion of the telomerase RNA component (TR) in the zebrafish results in impaired myelopoiesis, despite normal development of haematopoietic stem cells (HSCs). The neutropenia caused by TR depletion is independent of telomere length and telomerase activity. Genetic analysis shows that TR modulates the myeloid–erythroid fate decision by controlling the levels of the master myeloid and erythroid transcription factors spi1 and gata1, respectively. The alteration in spi1 and gata1 levels occurs through stimulation of gcsf and mcsf. Our model of TR deficiency in the zebrafish illuminates the non-canonical roles of TR, and could establish therapeutic targets for DC.

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