Resnick, Tamar D. et al. (2011) International Worm Meeting "Regulation and function of the let-7-related miRNA miR-48 in developmental timing."

Werre, Brittany, Resnick, Tamar D., Rougvie, Ann E.

[International Worm Meeting, 2011]

The heterochronic genes of C. elegans regulate temporal development, ensuring that developmental events proceed in correct sequence and at appropriate times. These genes, along with spatial and sexual regulators, are essential for proper patterning of the adult animal and include the first-identified miRNA genes, lin-4 and let-7. Loss of function of these miRNAs leads to reiteration of certain developmental events and delay of adult tissue differentiation, referred to as a "retarded" phenotype. let-7 miRNA shares identity at its 5' end with several other miRNAs including miR-48, miR-241, and miR-84, suggesting that they may target an overlapping set of mRNAs. These let-7-related miRNAs are expressed earlier in development than is let-7. Individual deletion of these genes results in only mild defects, however a triple deletion leads to a strong retarded phenotype, indicating that these miRNAs function redundantly. Inappropriately early and elevated expression of mir-48 caused by regulatory mutations leads to "precocious" phenotypes in which certain developmental patterns are skipped and subsequent events occur too early, underscoring the importance of proper temporal control of these miRNAs. We have taken advantage of the heterochronic gene pathway as a robust model for understanding regulation of miRNA expression and the relationships of related miRNAs. We are analyzing the cis-regulatory elements required for proper expression of miR-48 and miR-241, which is located approximately 1.8 kb upstream. Using mosSCI methods, we have generated lines with single copy transgenes inserted into a consistent, characterized genomic site. We are examining the effects of cis-regulatory mutations on the mir-241/mir-48 locus using qPCR to quantify mature miRNA levels directly and phenotypic analysis to determine consequences for developmental timing. To identify additional genes involved in developmental timing and miRNA expression or function, we screened for suppressors of precocious phenotypes arising from mir-48 over-expression from multicopy transgenic arrays. Among the suppressors recovered were 5 alleles of the heterochronic gene lin-66, which has been suggested to regulate LIN-28 in parallel with the let-7-family miRNAs. We are investigating the mechanism of this suppression by lin-66, including direct testing of whether it is mediated by LIN-28 modulation.

Daul, Aric et al. (2013) International Worm Meeting "Caenorhabditis Genetics Center."

Werre, Brittany, Rougvie, Ann E., Daul, Aric, Knott, Julie, Stiernagle, Theresa

[International Worm Meeting, 2013]

The Caenorhabditis Genetics Center (CGC), supported by the National Institutes of Health - Office of Research Infrastructure Programs (NIH-ORIP) and housed at the University of Minnesota, supplies Caenorhabditis strains and information to researchers throughout the world. The CGC has also initiated a small research component aimed at enhancing the genetic tool-kit available to C. elegans researchers. The CGC continues its duties of acquiring, maintaining and distributing worm stocks. There are now over 17,512 different strains in the collection. We strive to have at least one allele of every published gene and all chromosome rearrangements, duplications and deficiencies. Selected multiple-mutant stocks and transgenic strains are also available including strains that express various fluorescent protein reporter fusions. Greater than two thousand whole-genome sequenced strains, obtained from the Million Mutation Project and other sources, are available and have proved popular. The CGC also has stocks of nematode species closely related to C. elegans and bacterial strains necessary for nematode growth. A searchable strains list, including information about CGC stocks, is accessible either through the CGC website (www.cbs.umn.edu/CGC/) or through WormBase. Requests for strains should be made via the on-line ordering system available through our website. As mandated by NIH-ORIP, a small yearly user fee and charge per strain is assessed with each order. The CGC strongly encourages use of credit cards for payments. We provide yearly reports to the NIH with statistics that reflect our services to the worm community. A key tracked parameter is the number of published papers that acknowledge the CGC for providing strains. Please remember to acknowledge the CGC in your publications!.