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Comments on Guo, Yanwu et al. (2017) International Worm Meeting "clk-2 is a novel player in the C. elegans nonsense-mediated mRNA decay." (0)
Overview
Guo, Yanwu, & Ciosk, Rafal (2017). clk-2 is a novel player in the C. elegans nonsense-mediated mRNA decay presented in International Worm Meeting. Unpublished information; cite only with author permission.
Surveillance of aberrant RNAs is important for development and disease. To identify novel factors monitoring mRNA processing, we created a strain expressing a GFP reporter under the control of an aberrant 3'UTR. The reporter mRNA is degraded in wild-type animals. Following mutagenesis, we isolated mutants permitting expression of this reporter and found that most of them correspond to known components of the C. elegans nonsense-mediated mRNA decay pathway (NMD; encoded by the smg genes). The SMG proteins are conserved players in the NMD pathway, which is used to degrade aberrant mRNAs containing premature termination codons but also affects the stability many "normal" mRNAs. In worms, a previous study by Quinn et al reported NMD-mediated processing of pseudogenes. However, based on RNA sequencing datasets from different eukaryotes, the connection between NMD and pseudogenes appears to be nematode-specific. In addition to known NMD factors, our screen uncovered clk-2, previously implicated in DNA damage, as a novel player in the nematode NMD. CLK-2/TEL2 is a conserved protein, best known in humans for a function in telomere biology. Nevertheless, TEL2 was previously linked to NMD and our results suggest that CLK-2/TEL2 is a conserved player in the NMD pathway. The molecular mechanism of CLK-2 in NMD is currently under investigation.
Affiliation:
- Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland