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. 2011 Dec 17;2(11):918–939. doi: 10.1007/s13238-011-1119-x

A genome-wide RNAi screen identifies genes regulating the formation of P bodies in C. elegans and their functions in NMD and RNAi

Yinyan Sun 1, Peiguo Yang 1,2, Yuxia Zhang 1, Xin Bao 1, Jun Li 1, Wenru Hou 1, Xiangyu Yao 1, Jinghua Han 1, Hong Zhang 1,✉
PMCID: PMC4875186  PMID: 22180091

Abstract

Cytoplasmic processing bodies, termed P bodies, are involved in diverse post-transcriptional processes including mRNA decay, nonsense-mediated RNA decay (NMD), RNAi, miRNA-mediated translational repression and storage of translationally silenced mRNAs. Regulation of the formation of P bodies in the context of multicellular organisms is poorly understood. Here we describe a systematic RNAi screen in C. elegans that identified 224 genes with diverse cellular functions whose inactivations result in a dramatic increase in the number of P bodies. 83 of these genes form a complex functional interaction network regulating NMD. We demonstrate that NMD interfaces with many cellular processes including translation, ubiquitin-mediated protein degradation, intracellular trafficking and cytoskeleton structure.We also uncover an extensive link between translation and RNAi, with different steps in protein synthesis appearing to have distinct effects on RNAi efficiency. Moreover, the intracellular vesicular trafficking network plays an important role in the regulation of RNAi. A subset of genes enhancing P body formation also regulate the formation of stress granules in C. elegans. Our study offers insights into the cellular mechanisms that regulate the formation of P bodies and also provides a framework for system-level understanding of NMD and RNAi in the context of the development of multicellular organisms.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-011-1119-x and is accessible for authorized users.

Keywords: P body, stress granules, nonsense-mediated RNA decay (NMD), RNA interference, C. elegans

Electronic supplementary material

13238_2011_1119_MOESM1_ESM.pdf (531.1KB, pdf)

Supplementary material, approximately 531 KB.

13238_2011_1119_MOESM2_ESM.xls (189.5KB, xls)

Supplementary material, approximately 189 KB.

Footnotes

These authors contributed equally to the work.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-011-1119-x and is accessible for authorized users.

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Supplementary Materials

13238_2011_1119_MOESM1_ESM.pdf (531.1KB, pdf)

Supplementary material, approximately 531 KB.

13238_2011_1119_MOESM2_ESM.xls (189.5KB, xls)

Supplementary material, approximately 189 KB.

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