Upregulation of the let-7 microRNA with precocious development in lin-12/Notch hypermorphic Caenorhabditis elegans mutants |
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Authors: | Solomon Aharon Mian Yousaf Ortega-Cava Cesar Liu Victor Won Tat Gurumurthy Channabasavaiah Basavaraju Naramura Mayumi Band Vimla Band Hamid |
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Affiliation: | a Division of Molecular Oncology, Evanston Northwestern Healthcare Research Institute and Department of Medicine, Feinberg School of Medicine, USA b Division of Cancer Biology, Evanston Northwestern Healthcare Research Institute and Department of Medicine, Feinberg School of Medicine, USA c Department of Biochemistry, Molecular Biology and Cell Biology, Weinberg College of Arts and Sciences, Northwestern University, Evanston IL, 60201, USA |
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Abstract: | The lin-12/Notch signaling pathway is conserved from worms to humans and is a master regulator of metazoan development. Here, we demonstrate that lin-12/Notch gain-of-function (gf) animals display precocious alae at the L4 larval stage with a significant increase in let-7 expression levels. Furthermore, lin-12(gf) animals display a precocious and higher level of let-7 gfp transgene expression in seam cells at L3 stage. Interestingly, lin-12(gf) mutant rescued the lethal phenotype of let-7 mutants similar to other known heterochronic mutants. We propose that lin-12/Notch signaling pathway functions in late developmental timing, upstream of or in parallel to the let-7 heterochronic pathway. Importantly, the human microRNA let-7a was also upregulated in various human cell lines in response to Notch1 activation, suggesting an evolutionarily conserved cross-talk between let-7 and the canonical lin-12/Notch signaling pathway. |
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Keywords: | Heterochronic genes Developmental timing lin-12/Notch let-7 lin-41 microRNA molting Cell fate Seam cells |
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