Drosophila Suppressor of Sable Protein [Su(s)] Promotes Degradation of Aberrant and Transposon-Derived RNAs

Abstract

RNA-binding proteins act at various stages of gene expression to regulate and fine-tune patterns of mRNA accumulation. One protein in this class is Drosophila Su(s), a nuclear protein that has been previously shown to inhibit the accumulation of mutant transcripts by an unknown mechanism. Here, we have identified several additional RNAs that are downregulated by Su(s). These Su(s) targets include cryptic wild-type transcripts from the developmentally regulated Sgs4 and ng1 genes, noncoding RNAs derived from tandemly repeated αβ/αγ elements within an Hsp70 locus, and aberrant transcripts induced by Hsp70 promoter transgenes inserted at ectopic sites. We used the αβ RNAs to investigate the mechanism of Su(s) function and obtained evidence that these transcripts are degraded by the nuclear exosome and that Su(s) promotes this process. Furthermore, we showed that the RNA binding domains of Su(s) are important for this effect and mapped the sequences involved to a 267-nucleotide region of an αβ element. Taken together, these results suggest that Su(s) binds to certain nascent transcripts and stimulates their degradation by the nuclear exosome.

ACKNOWLEDGMENTS

We thank the following individuals for providing materials used in this study: S. Artavanis-Tsakonas, A. Hofmann, and J. Lis for fly stocks; A. Greenleaf and G. Dreyfuss for antibodies; and S. Beckendorf, R. Duronio, S. Lakhotia, and J. Lis for plasmids. We thank A. Hutchins, M. Peifer, and the reviewers for providing helpful comments on the manuscript.

This work was supported by grants MCB-0111821, MCB-0417019, and MCB-0517103 from the National Science Foundation.