C. elegans microRNAs

Abstract

MicroRNAs (miRNAs) are small, non-coding regulatory RNAs found in many phyla that control such diverse events as development, metabolism, cell fate and cell death. They have also been implicated in human cancers. The C. elegans genome encodes hundreds of miRNAs, including the founding members of the miRNA family lin-4 and let-7. Despite the abundance of C. elegans miRNAs, few miRNA targets are known and little is known about the mechanism by which they function. However, C. elegans research continues to push the boundaries of discovery in this area. lin-4 and let-7 are the best understood miRNAs. They control the timing of adult cell fate determination in hypodermal cells by binding to partially complementary sites in the mRNA of key developmental regulators to repress protein expression. For example, lin-4 is predicted to bind to seven sites in the lin-14 3' untranslated region (UTR) to repress LIN-14, while let-7 is predicted to bind two let-7 complementary sites in the lin-41 3' UTR to down-regulate LIN-41. Two other miRNAs, lsy-6 and mir-273, control left-right asymmetry in neural development, and also target key developmental regulators for repression. Approximately one third of the C. elegans miRNAs are differentially expressed during development indicating a major role for miRNAs in C. elegans development. Given the remarkable conservation of developmental mechanism across phylogeny, many of the principles of miRNAs discovered in C. elegans are likely to be applicable to higher animals.

The control of developmental phase transitions in plants

“…As a matter of fact, the very first miRNAs isolated from Caenorhabditis elegans, lin-4 and let-7, have been shown to play important roles during C. elegans postembryonic development (Kato and Slack, 2008;Vella and Slack, 2005). In brief, lin-4 and one of the targets of lin-4, LIN-14, are required for the larval stage 1 (L1)-to-L2 transition.…”

A review of transgenerational epigenetics for RNAi, longevity, germline maintenance and olfactory imprinting in Caenorhabditis elegans

“…What other mechanisms are yet to be uncovered? This review has only covered a subset of the research on mechanisms of transgenerational epigenetics that has been done using C. elegans; more detailed reviews can be found elsewhere (see Bagjin et al, 2012;Benayoun and Brunet, 2012;Billi et al, 2013;Brasset and Chambeyron, 2013;Kelly, 2014;Feng and Guang, 2013;Lim and Brunet, 2013;Vella and Slack, 2005;Wenzel et al, 2011). This is a rich field of study, and it is clear that C. elegans offers unique opportunities to rapidly uncover the molecular machinery regulating this amazing process.…”

“…These studies showed that miRNAs negatively regulated their target mRNAs by binding to target sites in the 3′ UTRs. Since the original discovery of RNAi in C. elegans (Fire et al, 1998), and the discovery of miRNAs (Lee et al, 1993;Reinhart et al, 2000), the field of small RNAs has exploded on to the genetic scene (for review, see Vella and Slack, 2005). In C. elegans, thousands of unique endogenous small RNAs have been identified; these small RNAs fall into three classes, based on size and function: (1) siRNAs (endo-siRNAs for endogenous RNAs and exo-siRNAs for exogenous RNAs), (2) miRNAs and (3) PIWI-interacting RNAs (where PIWI is P-element-induced wimpy testis; piRNAs) (Billi et al, 2013).…”

Analysis of the Hox epigenetic code

“…In addition, there are many complexes that exist in both C. elegans and humans such as micro RNAs lin-4 and let-7 which have been connected to many cancers [27] , and 153 kinase subfamilies which direct most cellular processes, particularly in signal transduction and coordination of complex pathways [28] . Similarities and homologs between both organisms are shown in Tables 2-5.…”