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Cell. 2013 Feb 28;152(5):957-68. doi: 10.1016/j.cell.2013.01.046. Epub 2013 Feb 14.

Stalled spliceosomes are a signal for RNAi-mediated genome defense.

Author information

1
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.

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.

PMID:
23415457
PMCID:
PMC3645481
DOI:
10.1016/j.cell.2013.01.046
[Indexed for MEDLINE]
Free PMC Article

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