Talk abstracts

Talk on Friday 02:00-02:15pm submitted by Sarah Geisler

Decapping regulates non-coding RNA-dependent histone modification in Saccharomyces cerevisiae

Sarah Geisler (Center for RNA Molecular Biology, Case Western Reserve University), Lisa Lojek (Center for RNA Molecular Biology, Case Western Reserve University), Jeff Coller (Center for RNA Molecular Biology, Case Western Reserve University)

Abstract:
In this study we document that decapping-dependent turnover is the major pathway of decay for key non-coding RNAs (ncRNAs) generated from the GAL and PHO84 loci in budding yeast. Additionally, we show at the GAL locus, decapping of the regulatory ncRNA (GAL1 uCUT) is required for efficient expression of the GAL1 mRNA.

The role of the decapping enzyme in controlling cytoplasmic mRNA levels is well documented. In the cytoplasm, mRNA turnover is initiated by the loss of the poly(A) tail, followed by decapping, and subsequent 5’-3’ exoribonuclease digestion. The majority of RNA polymerase II transcripts receive a 5’ cap structure, and in recent years it has become clear that RNA polymerase II (pol II) transcribes more than just mRNAs. Indeed, transcription by pol II is pervasive with estimates of RNA transcripts originating from up to 80% of the non-repetitive sequence of the S. cerevisiae genome (1). Moreover, close examination of the transcriptional output of yeast cells has revealed the existence of cryptic unstable transcripts (CUTs) that are virtually undetectable in wild-type cells, but accumulate in the absence of the nuclear exosome (2). Here we document that the destruction of known CUTs are also controlled by the decapping enzyme. In a novel decapping pathway, decay of these CUTs is dependent on the catalytic activity of the decapping enzyme, but is independent of deadenylation as well as known decapping regulators. Additionally, we show that stabilization of the ncRNA by the loss of the decapping enzyme results in a severe impairment in neighboring gene expression. Furthermore, we show decapping-dependent decay of a key ncRNA influences the chromatin state of neighboring genes, thereby impacting the overall gene expression profile. These data highlight a novel cellular role for the mRNA decapping enzyme in impacting the overall architecture of the transcriptome.

References:
1. Nagalakshmi, U., et al., The transcriptional landscape of the yeast genome defined by RNA sequencing. Science, 2008. 320(5881): p. 1344-9.
2. Wyers, F., et al., Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell, 2005. 121(5): p. 725-37.

Keywords: non-coding RNA, decapping, histone modification