title: Functional relevance of "seed" and "non-seed" sequences in microRNA-mediated promotion of C. elegans developmental progression.
abstract: The founding heterochronic microRNAs, lin-4 and let-7, together with their validated targets and well-characterized phenotypes in C. elegans, offer an opportunity to test functionality of microRNAs in a developmental context. In this study, we defined sequence requirements at the microRNA level for these two microRNAs, evaluating lin-4 and let-7 mutant microRNAs for their ability to support temporal development under conditions where the wild-type lin-4 and let-7 gene products are absent. For lin-4, we found a strong requirement for seed sequences, with function drastically affected by several central mutations in the seed sequence, while rescue was retained by a set of mutations peripheral to the seed. let-7 rescuing activity was retained to a surprising degree by a variety of central seed mutations, while several non-seed mutant effects support potential noncanonical contributions to let-7 function. Taken together, this work illustrates both the functional partnership between seed and non-seed sequences in mediating C. elegans temporal development and a diversity among microRNA effectors in the contributions of seed and non-seed regions to activity.
authors.affiliation: Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Huibin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Artiles
authors.affiliation: Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Andrew Z
authors.initials: AZ
authors.lastname: Fire
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010641:Phenotype
chemical_list: D029742:Caenorhabditis elegans Proteins; D035683:MicroRNAs
keywords: C. elegans; let-7; lin-4; microRNA; seed