RNAi Discussion Group
Thursday, February 16, 2006
Presented by the RNAi Discussion Group
Organizer: Eric Lai, Sloan Kettering Institute
The goal of this group is to provide a forum for New York–area scientists engaged in research into the biology, biochemistry, and applications of RNAi silencing to meet regularly to discuss advances in this exciting new field and to promote interinstitutional and interdisciplinary dialogue. Topics of discussion include regulation of RNAi gene expression, mechanistic studies into RNAi action, regulation of gene expression by siRNAs, RNAi in health and disease, and applied uses of technologies related to RNAi.
5:00 - 7:30 Presentations
Asa Abeliovich, Columbia University, "miRNA in ES Cell Differentiation."
Rui Yi, Rockefeller University, "Morphogenesis in Skin is Governed by Discrete Sets of Differentially Expressed microRNAs."
Antonio Giraldez, Harvard University, "Zebrafish microRNA miR-430 Promotes Deadenylation and Clearance of Maternal mRNAs."
"Morphogenesis in Skin is Governed by Discrete Sets of Differentially Expressed microRNAs"
During embryogenesis, multipotent progenitors within the single-layered surface epithelium differentiate to form the epidermis and its appendages. Here, we show that microRNAs play an essential role in orchestrating these events. We cloned more than 100 miRNAs from skin and show that epidermis and hair follicles differentially express discrete miRNA families. To explore the functional significance of this finding, we conditionally targeted Dicer gene ablation in embryonic skin progenitors. Within the first week following loss of miRNA expression, cell fate specification and differentiation are not markedly impaired, and in the interfollicular epidermis, apoptosis is not dramatically increased. Remarkably however, developing hair germs evaginate rather than invaginate, thereby perturbing the epidermal organization. These findings not only reveal the hitherto unappreciated existence of miRNAs in skin, but also their characterization, differential expression and differential importance in the morphogenesis of epithelial tissues within this vital organ.
"Zebrafish microRNA miR-430 Promotes Deadenylation and Clearance of Maternal mRNAs"
MicroRNAs comprise 1-3% of all vertebrate genes, but their in vivo functions and mechanisms of action remain largely unknown. Zebrafish miR-430 is expressed at the onset of zygotic transcription and regulates morphogenesis during early development. Using a microarray approach and in vivo target validation, we find that miR-430 directly regulates several hundred target mRNAs. Targets are highly enriched for maternal mRNAs that accumulate in the absence of miR-430. We also show that miR-430 accelerates the deadenylation of target mRNAs. These results suggest that miR-430 facilitates the deadenylation and clearance of maternal mRNAs during early embryogenesis.