예쁜 꼬마 선충에서 RNA 품질관리 메커니즘의 노화 조절 연구

Abstract

Orchestrated protein and DNA quality control plays important role in preventing premature aging and promoting longevity in many species. Recent studies showed that RNA quality control is also crucial for longevity. We previously reported that nonsense-mediated mRNA decay (NMD), one of the key RNA quality control systems, mediates longevity of various long-lived mutant C. elegans, such as reduced insulin/IGF-1 signaling (IIS) mutant. However, mechanisms by which NMD contributes to longevity or is enhanced by reduced IIS remain elusive. In addition, the role of non-stop decay (NSD) and no-go decay (NGD), the remaining two RNA quality control mechanisms, in aging is unknown. Here, I aimed to identify novel NMD regulators that regulate aging through genome-wide RNAi and mutagenesis screens and to investigate aging regulatory roles of NSD and NGD. I showed that inhibition of NSD or NGD factors also reduce lifespan similar to that of NMD. Moreover, from the genome-wide and mutagenesis screens, I identified 5 RNAi clones and isolated 20 mutants that altered GFP expression of the NMD-responsive reporter. These multiple rounds of genetic screens followed by functional characterization may uncover how various RNA quality controls modulate organismal aging.