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07.08.17 Miska lab tease out role of RNA helicase Aquarius in heritable transcriptional silencing

last modified Sep 19, 2017 10:03 PM
In this Developmental Cell paper, Akay et al. show that Aquarius/EMB-4 is a direct and essential link between small RNA pathways and the transcriptional machinery in C. elegans
07.08.17 Miska lab tease out role of RNA helicase Aquarius in heritable transcriptional silencing

Graphical abstract from the paper

The Helicase Aquarius/EMB-4 Is Required to Overcome Intronic Barriers to Allow Nuclear RNAi Pathways to Heritably Silence Transcription

Akay A et al (2017) Dev Cell 42(3): 241-255.e6. DOI: 10.1016/ j.devcel.2017.07.002

 

Highlights from the paper

  • Nuclear Argonaute HRDE-1 physically interacts with the helicase EMB-4/AQR
  • EMB-4/AQR is required for heritable silencing of genes and transposable elements
  • Intronic sequences form a barrier to nuclear RNAi pathway
  • EMB-4/AQR removes intronic barriers for efficient silencing by HRDE-1


Summary from the paper

Small RNAs play a crucial role in genome defense against transposable elements and guide Argonaute proteins to nascent RNA transcripts to induce co-transcriptional gene silencing. However, the molecular basis of this process remains unknown.

Here, we identify the conserved RNA helicase Aquarius/EMB-4 as a direct and essential link between small RNA pathways and the transcriptional machinery in Caenorhabditis elegans. Aquarius physically interacts with the germline Argonaute HRDE-1. Aquarius is required to initiate small-RNA-induced heritable gene silencing. HRDE-1 and Aquarius silence overlapping sets of genes and transposable elements. Surprisingly, removal of introns from a target gene abolishes the requirement for Aquarius, but not HRDE-1, for small RNA-dependent gene silencing.

We conclude that Aquarius allows small RNA pathways to compete for access to nascent transcripts undergoing co-transcriptional splicing in order to detect and silence transposable elements. Thus, Aquarius and HRDE-1 act as gatekeepers coordinating gene expression and genome defense.

 

Extracts from paper reproduced under CC BY 4.0.

 

Read more about research in the Miska lab.

Watch Eric Miska describe his research on RNA.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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