Current Biology
Volume 21, Issue 6, 22 March 2011, Pages 449-459
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Article
EGO-1, a C. elegans RdRP, Modulates Gene Expression via Production of mRNA-Templated Short Antisense RNAs

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Summary

Background

The development of the germline in Caenorhabditis elegans is a complex process involving the regulation of thousands of genes in a coordinated manner. Several genes required for small RNA biogenesis and function are among those required for the proper organization of the germline. EGO-1 is a putative RNA-directed RNA polymerase (RdRP) that is required for multiple aspects of C. elegans germline development and efficient RNA interference (RNAi) of germline-expressed genes. RdRPs have been proposed to act through a variety of mechanisms, including the posttranscriptional targeting of specific mRNAs, as well as through a direct interaction with chromatin. Despite extensive investigation, the molecular role of EGO-1 has remained enigmatic.

Results

Here we use high-throughput small RNA and messenger RNA sequencing to investigate EGO-1 function. We found that EGO-1 is required to produce a distinct pool of small RNAs antisense to a number of germline-expressed mRNAs through several developmental stages. These potential mRNA targets fall into distinct classes, including genes required for kinetochore and nuclear pore assembly, histone-modifying activities, and centromeric proteins. We also found several RNAi-related genes to be targets of EGO-1. Finally, we show a strong association between the loss of small RNAs and the rise of mRNA levels in ego-1(−) animals.

Conclusions

Our data support the conclusion that EGO-1 produces triphosphorylated small RNAs derived from mRNA templates and that these small RNAs modulate gene expression through the targeting of their cognate mRNAs.

Highlights

▸ EGO-1 is responsible for producing small RNAs antisense to hundreds of genes ▸ EGO-1-dependent small RNAs can act by modulating mRNA abundance levels ▸ EGO-1 targets include genes required for kinetochore and nuclear pore assembly ▸ Target sets enriched for genes with histone-modifying and RNAi-related functions

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