Considering the vital and fundamental nature of RNA silencing functions, it is surprising that relatively few RNA silencing genes are required for viability or fertility, suggesting a functional overlap of RNA silencing activities. Genetic defects in some members of these pathways can lead to developmental or environmentally-influenced phenotypes in Caenorhabditis elegans. Hundreds of genes have been implicated in RNA silencing using forward genetic and RNAi-based screens, which is a testament to the scope of these mechanisms in cells. RNA silencing pathways include RNA interference (RNAi) mechanisms that are triggered when dsRNA is provided to cells.
RNA silencing mechanisms serve as cellular sentinels, providing fundamental anti-foreign genome defense activities that protect cells against transposon mobilization and organisms against systemic viral infection. RNA silencing is a term commonly used to describe the multiple, overlapping, RNA-directed pathways that are used by cells to regulate gene expression and chromatin functions. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. Publication costs were supported by the University of Kansas General Research Fund allocation #2301303-906. 0951296 to LT by the United States Educational Foundation in Pakistan/Fulbright Scholarship Program ( and ) to NA and the KU Honors Program ( ) to WYA. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This work was supported by a grant from the National Science Foundation ( Grant No. Received: JAccepted: OctoPublished: November 28, 2012Ĭopyright: © 2012 Asad et al.
Iowa State University, United States of America These observations highlight the potential for unanticipated mutations, coupled with genetic and environmental phenomena, to enhance or suppress the effects of known mutations and cause variation between wild-type strains.Ĭitation: Asad N, Aw WY, Timmons L (2012) Natural and Unanticipated Modifiers of RNAi Activity in Caenorhabditis elegans. We also report experimental, environmental, and genetic conditions that can complicate phenotypic analysis of RNAi pathway defects.
In so doing, we uncovered a mutation that arose de novo in an existing strain, which initially frustrated our phenotypic analysis. Our objective was to identify and analyze single locus genetic defects leading to RNAi resistance in isogenic strains of Caenorhabditis elegans.
Low frequency alleles or mutations with modest effects on phenotypes can contribute to natural variation, and it has proven possible for such sequences to become fixed by adapted evolutionary enrichment and identified by resequencing. Sequence differences may arise from replication errors, transposon mobilization, meiotic gene conversion, or environmental or chemical assault on the genome. Organisms used as model genomics systems are maintained as isogenic strains, yet evidence of sequence differences between independently maintained wild-type stocks has been substantiated by whole-genome resequencing data and strain-specific phenotypes.
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