Leading science, pioneering therapies
CRM Publications

The miR-144/451 locus is required for erythroid homeostasis.

TitleThe miR-144/451 locus is required for erythroid homeostasis.
Publication TypeJournal Article
Year of Publication2010
AuthorsRasmussen KD, Simmini S, Abreu-Goodger C, Bartonicek N, Di Giacomo M, Bilbao-Cortes D, Horos R, Von Lindern M, Enright AJ, O'Carroll D
JournalJ Exp Med
Volume207
Issue7
Pagination1351-8
Date Published2010 Jul 5
ISSN1540-9538
KeywordsAnemia, Animals, Argonaute Proteins, Cell Differentiation, Cell Lineage, Erythroblasts, Erythroid Cells, Erythropoiesis, Eukaryotic Initiation Factor-2, Gene Expression Regulation, Developmental, Genetic Loci, Homeostasis, Hyperplasia, Mice, Mice, Inbred C57BL, MicroRNAs
Abstract

The process of erythropoiesis must be efficient and robust to supply the organism with red bloods cells both under condition of homeostasis and stress. The microRNA (miRNA) pathway was recently shown to regulate erythroid development. Here, we show that expression of the locus encoding miR-144 and miR-451 is strictly dependent on Argonaute 2 and is required for erythroid homeostasis. Mice deficient for the miR-144/451 cluster display a cell autonomous impairment of late erythroblast maturation, resulting in erythroid hyperplasia, splenomegaly, and a mild anemia. Analysis of gene expression profiles from wild-type and miR-144/451-deficient erythroblasts revealed that the miR-144/451 cluster acts as a "tuner" of gene expression, influencing the expression of many genes. MiR-451 imparts a greater impact on target gene expression than miR-144. Accordingly, mice deficient in miR-451 alone exhibited a phenotype indistinguishable from miR-144/451-deficient mice. Thus, the miR-144/451 cluster tunes gene expression to impart a robustness to erythropoiesis that is critical under conditions of stress.

DOI10.1084/jem.20100458
Alternate JournalJ. Exp. Med.
PubMed ID20513743
PubMed Central IDPMC2901075
Publication institute
Other