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Stalled Spliceosomes Are a Signal for RNAi-Mediated Genome Defense

Author(s)
Dumesic, Phillip A.; Natarajan, Prashanthi; Chen, Changbin; Drinnenberg, Ines A.; Schiller, Benjamin J.; Thompson, James; Moresco, James J.; Yates, John R.; Madhani, Hiten D.; Bartel, David; ... Show more Show less
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Abstract
Using the yeast Cryptococcus neoformans, we describe a mechanism by which transposons are initially targeted for RNAi-mediated genome defense. We show that intron-containing mRNA precursors template siRNA synthesis. We identify a Spliceosome-Coupled And Nuclear RNAi (SCANR) complex required for siRNA synthesis and demonstrate that it physically associates with the spliceosome. We find that RNAi target transcripts are distinguished by suboptimal introns and abnormally high occupancy on spliceosomes. Functional investigations demonstrate that the stalling of mRNA precursors on spliceosomes is required for siRNA accumulation. Lariat debranching enzyme is also necessary for siRNA production, suggesting a requirement for processing of stalled splicing intermediates. We propose that recognition of mRNA precursors by the SCANR complex is in kinetic competition with splicing, thereby promoting siRNA production from transposon transcripts stalled on spliceosomes. Disparity in the strength of expression signals encoded by transposons versus host genes offers an avenue for the evolution of genome defense.
Date issued
2013-02
URI
http://hdl.handle.net/1721.1/116327
Department
Massachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Journal
Cell
Publisher
Elsevier BV
Citation
Dumesic, Phillip A. et al. “Stalled Spliceosomes Are a Signal for RNAi-Mediated Genome Defense.” Cell 152, 5 (February 2013): 957–968 © 2013 Elsevier Inc
Version: Author's final manuscript
ISSN
0092-8674
1097-4172

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