title: The mir-51 family of microRNAs functions in diverse regulatory pathways in Caenorhabditis elegans.
abstract: The mir-51 family of microRNAs (miRNAs) in C. elegans are part of the deeply conserved miR-99/100 family. While loss of all six family members (mir-51-56) in C. elegans results in embryonic lethality, loss of individual mir-51 family members results in a suppression of retarded developmental timing defects associated with the loss of alg-1. The mechanism of this suppression of developmental timing defects is unknown. To address this, we characterized the function of the mir-51 family in the developmental timing pathway. We performed genetic analysis and determined that mir-51 family members regulate the developmental timing pathway in the L2 stage upstream of hbl-1. Loss of the mir-51 family member, mir-52, suppressed retarded developmental timing defects associated with the loss of let-7 family members and lin-46. Enhancement of precocious defects was observed for mutations in lin-14, hbl-1, and mir-48(ve33), but not later acting developmental timing genes. Interestingly, mir-51 family members showed genetic interactions with additional miRNA-regulated pathways, which are regulated by the let-7 and mir-35 family miRNAs, lsy-6, miR-240/786, and miR-1. Loss of mir-52 likely does not suppress miRNA-regulated pathways through an increase in miRNA biogenesis or miRNA activity. We found no increase in the levels of four mature miRNAs, let-7, miR-58, miR-62 or miR-244, in mir-52 or mir-52/53/54/55/56 mutant worms. In addition, we observed no increase in the activity of ectopic lsy-6 in the repression of a downstream target in uterine cells in worms that lack mir-52. We propose that the mir-51 family functions broadly through the regulation of multiple targets, which have not yet been identified, in diverse regulatory pathways in C. elegans.
authors.affiliation: Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin, United States of America.
authors.forename: John L
authors.initials: JL
authors.lastname: Brenner
authors.forename: Benedict J
authors.initials: BJ
authors.lastname: Kemp
authors.forename: Allison L
authors.initials: AL
authors.lastname: Abbott
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D018507:Gene Expression Regulation, Developmental; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D035683:MicroRNAs; C474488:let-7 microRNA, C elegans