hsa-miR-144

thalassemia

Relationship type:

Causal

Detection method for miRNA expression:

Northern blot, qRT-PCR etc

down-regulated

Validated targets of miRNA from the reference:

Klfd

Validated targets of miRNA from TarBase:

unknown : More...

Description:

Precise transcriptional control of developmental stage-specific expression and switching of alpha- and beta-globin genes is significantly important to understand the general principles controlling gene expression and the pathogenesis of thalassemia. Although transcription factors regulating beta-globin genes have been identified, little is known about the microRNAs and trans-acting mechanism controlling alpha-globin genes transcription.Here, we show that an erythroid lineage-specific microRNA gene, miR-144, expressed at specific developmental stages during zebrafish embryogenesis, negatively regulates the embryonic alpha-globin, but not embryonic beta-globin genes expression, through physiologically targeting klfd, an erythroid-specific Kruppel-like transcription factor. Klfd selectively binds to the CACCC boxes in the promoters of both alpha-globin and miR-144 genes to activate their transcriptions, thus forming a negative feedback circuitry to fine-tune the expression of embryonic alpha-globin gene. The selective effect of miR-144-Klfd pathway on globin gene regulation may thereby constitute a novel therapeutic target for improving the clinical outcome of patients with thalassemia.

Reference:

Mir-144 selectively regulates embryonic {alpha}-hemoglobin synthesis during primitive erythropoiesis. | PMID:18941117
Fu YF, Du TT, Dong M, Zhu KY, Jing CB, Zhang Y, Wang L, Fan HB, Chen Y, Jin Y, Yue GP, Chen SJ, Chen Z, Huang QH, Jing Q, Deng M, Liu TX.
Blood. 2008 Oct 21. [Epub ahead of print]