MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling.
MicroRNAs (miRNAs) are genomically encoded small RNAs that hybridize with messenger RNAs, resulting in degradation or translational inhibition of targeted transcripts. The potential for miRNAs to regulate cell-lineage determination or differentiation from pluripotent progenitor or stem cells is unknown. Here, we show that microRNA1 (miR-1) is an ancient muscle-specific gene conserved in sequence and expression in Drosophila. Drosophila miR-1 (dmiR-1) is regulated through a serum response factor-like binding site in cardiac progenitor cells. Loss- and gain-of-function studies demonstrated a role for dmiR-1 in modulating cardiogenesis and in maintenance of muscle-gene expression. We provide in vivo evidence that dmiR-1 targets transcripts encoding the Notch ligand Delta, providing a potential mechanism for the expansion of cardiac and muscle progenitor cells and failure of progenitor cell differentiation in some dmiR-1 mutants. These findings demonstrate that dmiR-1 may "fine-tune" critical steps involved in differentiation of cardiac and somatic muscle progenitors and targets a pathway required for progenitor cell specification and asymmetric cell division.
Kwon
Chulan
C
Gladstone Institute of Cardiovascular Disease and Department of Pediatrics, University of California, 1650 Owens Street, San Francisco, CA 94158.
Han
Zhe
Z
Olson
Eric N
EN
Srivastava
Deepak
D
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D035683:MicroRNAs; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D011995:Recombination, Genetic; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D013997:Time Factors; D014162:Transfection; D019076:Transgenes; D015854:Up-Regulation
D020413:3' Untranslated Regions; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D051880:Receptors, Notch; C064045:delta protein; D049452:Green Fluorescent Proteins