microRNAs regulate gene expression through interaction with an Argonaute protein. While some members of this protein family retain an enzymatic activity capable of cleaving RNA molecules complementary to Argonaute-bound small RNAs, the role of the slicer residues in the canonical microRNA pathway is still unclear in animals. To address this, we created Caenorhabditis elegans strains with mutated slicer residues in the endogenous ALG-1 and ALG-2, the only two slicing Argonautes essential for the miRNA pathway in this animal model.
View Article and Find Full Text PDFThe Anaphase Promoting Complex (APC) regulates the transition from metaphase to anaphase during cell division and is important to prevent defects in chromosome segregation. In a recent temperature sensitive genetic screen looking for further genes involved in fertilization, we isolated a new temperature sensitive allele of . We also sequenced a previously identified allele that did not previously have an annotated sequence.
View Article and Find Full Text PDFFertilization is a fundamental process in sexual reproduction during which gametes fuse to combine their genetic material and start the next generation in their life cycle. Fertilization involves species-specific recognition, adhesion, and fusion between the gametes. In mammals and other model species, some proteins are known to be required for gamete interactions and have been validated with loss-of-function fertility phenotypes.
View Article and Find Full Text PDFInfertility and development of contraceptive methods have profound societal affects; however, the genetic mechanisms underlying this are still largely unknown. Here, we describe how using the small worm has helped us to discover the genes involved in these processes. Nobel Laureate Sydney Brenner established the nematode worm as a genetic model system with a powerful ability to discover genes in many biological pathways through mutagenesis.
View Article and Find Full Text PDFComplementary forward and reverse genetic approaches in several model systems have resulted in a recent burst of fertilization gene discovery. The number of genetically validated gamete surface molecules have more than doubled in the last few years. All the genetically validated sperm fertilization genes encode transmembrane or secreted molecules.
View Article and Find Full Text PDFmicroRNAs regulate gene expression through interaction with an Argonaute protein family member. While some members of this protein family retain an enzymatic activity capable of cleaving RNA molecules complementary to Argonaute-bound small RNAs, the role of the slicing activity in the canonical microRNA pathway is still unclear in animals. To address the importance of slicing Argonautes in animals, we created strains, carrying catalytically dead endogenous ALG-1 and ALG-2, the only two slicing Argonautes essential for the miRNA pathway in this animal model.
View Article and Find Full Text PDFPosttranscriptional regulation of gene expression, typically effected by RNA-binding proteins, microRNAs (miRNAs), and translation initiation factors, is essential for normal germ cell function. Numerous miRNAs have been detected in the germline; however, the functions of specific miRNAs remain largely unknown. Functions of miRNAs have been difficult to determine as miRNAs often modestly repress target mRNAs and are suggested to sculpt or fine tune gene expression to allow for the robust expression of cell fates.
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