Nature:科学家在酿酒酵母中识别出反义ncRNA

2011-07-11 10:03 · Elijah

背景:来自多个方面证据表明,非编码RNA (ncRNA)在真核细胞的基因调控中有重要作用。

背景:来自多个方面证据表明,非编码RNA (ncRNA)在真核细胞的基因调控中有重要作用。

研究进展:随着酿酒酵母全基因组精细测序完成,识别出反义ncRNA,5' RNA-decay通道中的Xrn1 RNA核酸外切酶能破坏它们的稳定性。这些“对Xrn1敏感的、不稳定的转录体”(称之为XUT)似乎在基因抑制中发挥功能,并且可被三甲基化组蛋白H3K4所拮抗。

酿酒酵母中存在反义ncRNA

酿酒酵母中存在反义ncRNA

生物探索推荐英文摘要

XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast

Abstract:  Non-coding (nc)RNAs are key players in numerous biological processes such as gene regulation, chromatin domain formation and genome stability1, 2. Large ncRNAs interact with histone modifiers3, 4, 5 and are involved in cancer development6, X-chromosome inactivation7 and autosomal gene imprinting8. However, despite recent evidence showing that pervasive transcription is more widespread than previously thought9, only a few examples mediating gene regulation in eukaryotes have been described10. In Saccharomyces cerevisiae, the bona-fide regulatory ncRNAs are destabilized by the Xrn1 5′–3′ RNA exonuclease11, 12 (also known as Kem1), but the genome-wide characterization of the entire regulatory ncRNA family remains elusive. Here, using strand-specific RNA sequencing (RNA-seq), we identify a novel class of 1,658 Xrn1-sensitive unstable transcripts (XUTs) in which 66% are antisense to open reading frames. These transcripts are polyadenylated and RNA polymerase II (RNAPII)-dependent. The majority of XUTs strongly accumulate in lithium-containing media, indicating that they might have a role in adaptive responses to changes in growth conditions. Notably, RNAPII chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) analysis of Xrn1-deficient strains revealed a significant decrease of RNAPII occupancy over 273 genes with antisense XUTs. These genes show an unusual bias for H3K4me3 marks and require the Set1 histone H3 lysine 4 methyl-transferase for silencing. Furthermore, abolishing H3K4me3 triggers the silencing of other genes with antisense XUTs, supporting a model in which H3K4me3 antagonizes antisense ncRNA repressive activity. Our results demonstrate that antisense ncRNA-mediated regulation is a general regulatory pathway for gene expression in S. cerevisiae.

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