The let-7 microRNA (miRNA) regulates cellular differentiation across many animal species. Loss of let-7 activity causes abnormal development in Caenorhabditis elegans and unchecked cellular proliferation in human cells, which contributes to tumorigenesis. These defects are due to improper expression of protein-coding genes normally under let-7 regulation. While some direct targets of let-7 have been identified, the genome-wide effect of let-7 insufficiency in a developing animal has not been fully investigated. Here we report the results of molecular and genetic assays aimed at determining the global network of genes regulated by let-7 in C. elegans. By screening for mis-regulated genes that also contribute to let-7 mutant phenotypes, we derived a list of physiologically relevant potential targets of let-7 regulation. Twenty new suppressors of the rupturing vulva or extra seam cell division phenotypes characteristic of let-7 mutants emerged. Three of these genes, opt-2, prmt-1, and T27D12.1, were found to associate with Argonaute in a let-7-dependent manner and are likely novel direct targets of this miRNA. Overall, a complex network of genes with various activities is subject to let-7 regulation to coordinate developmental timing across tissues during worm development.
Pubmed ID: 23516374 RIS Download
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Central data repository for nematode biology including complete genomic sequence, gene predictions and orthology assignments from range of related nematodes.Data concerning genetics, genomics and biology of C. elegans and related nematodes. Derived from initial ACeDB database of C. elegans genetic and sequence information, WormBase includes genomic, anatomical and functional information of C. elegans, other Caenorhabditis species and other nematodes. Maintains public FTP site where researchers can find many commonly requested files and datasets, WormBase software and prepackaged databases.
View all literature mentionsWeb tool to predict biological targets of miRNAs by searching for presence of conserved 8mer, 7mer and 6mer sites that match seed region of each miRNA. Nonconserved sites are also predicted and sites with mismatches in seed region that are compensated by conserved 3' pairing. Used to search for predicted microRNA targets in mammals.
View all literature mentionsCatalogs of predicted microRNA targets in worm (based on ce6 genome assembly), fly (dm3), mouse (mm9) and human (hg18). We follow standard seed parameter settings and consider seeds of length 6-8 bases, beginning at position 2 of the microRNA. No mismatches or loops are allowed, but a single G:U wobble is allowed in 7- or 8-mers. In genes missing a 3' UTR annotation, 500 bp (fly), 800 bp (human and mouse) or 300 bp (worm) downstream of the annotated end of the coding sequence were used as the predicted UTR. For each organism, a catalog with zero flank and with a flank of 3 and 15 bases upstream and downstream.
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