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Small RNAs

Endo-siRNAs truly endogenous

Nature Reviews Molecular Cell Biology volume 9, page 427 (2008)Cite this article

During RNA interference (RNAi), members of the Dicer family of proteins cleave double-stranded (ds) RNA of an endogenous or exogenous source into 21–24 nucleotide siRNAs. dsRNA cleavage is coupled to the loading of these siRNAs onto the RNA-induced silencing complex (RISC). The siRNA guides the RISC complex to the corresponding target mRNA, which is degraded through cleavage by Argonaute (AGO) proteins.

The groups of Greg Hannon and Hiroyuki Sasaki found a large number of both Piwi-interacting RNAs (piRNAs) and endo-siRNAs that corresponded to mRNAs or retrotransposons in growing oocytes. Endo-siRNAs were exclusively mapped to retrotransposons or other genomic regions that produce transcripts capable of forming dsRNA structures. The genomic sources of dsRNAs that generate endo-siRNAs included inverted repeat structures, sites of bidirectional transcription and antisense transcripts from various loci, including retrotransposons and pseudogenes. Loss of Dicer or AGO2 resulted in decreased levels of endo-siRNAs and increased levels of retrotransposon and protein-coding transcripts that are complementary to the endo-siRNAs. These findings reveal a role for endo-siRNAs in mammals and indicate that the RNAi pathway regulates both protein-coding transcripts and retrotransposons in mouse oocytes.

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ORIGINAL RESEARCH PAPERS

  1. Chung, W.-J. et al. Endogenous RNA interference provides a somatic defense against Drosophila transposons. Curr. Biol. 22 May 2008 (doi:10.1016/j.cub.2008.05.006)

  2. Czech, B. et al. An endogenous small interfering RNA pathway in Drosophila. Nature 7 May 2008 (doi:10.1038/nature07007)

  3. Ghildiyal, M. et al. Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells. Sciencexpress 10 April 2008 (doi:10.1126/science.1157396)

  4. Kawamura, Y. et al. Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells. Nature 7 May 2008 (doi:10.1038/nature06938)

  5. Okamura, K. et al. The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs. Nature 7 May 2008 (doi:10.1038/nature07015)

  6. Tam, O. H. et al. Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 10 April 2008 (doi:10.1038/nature06904)

  7. Watanabe, T. et al. Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 10 April 2008 (doi:10.1038/nature06908)

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Authors
  1. Ekat Kritikou
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Kritikou, E. Endo-siRNAs truly endogenous. Nat Rev Mol Cell Biol 9, 427 (2008). https://doi.org/10.1038/nrm2424

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  • DOI: https://doi.org/10.1038/nrm2424

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