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Cryptic introns in lncRNAs recruit conserved Pir2/ARS2 protein to promote gene repression

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Schizosaccharomyces pombe

PROVIDER: GSE135161 | GEO | 2020/04/07

REPOSITORIES: GEO

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Conserved protein Pir2<sup>ARS2</sup> mediates gene repression through cryptic introns in lncRNAs.

Project description:Long non-coding RNAs (lncRNAs) are components of epigenetic control mechanisms that ensure appropriate and timely gene expression. The functions of lncRNAs are often mediated through associated gene regulatory activities, but how lncRNAs are distinguished from other RNAs and recruit effector complexes is unclear. Here, we utilize the fission yeast Schizosaccharomyces pombe to investigate how lncRNAs engage silencing activities to regulate gene expression in cis. We find that invasion of lncRNA transcription into the downstream gene body incorporates a cryptic intron required for repression of that gene. Our analyses show that lncRNAs containing cryptic introns are targeted by the conserved Pir2ARS2 protein in association with splicing factors, which recruit RNA processing and chromatin-modifying activities involved in gene silencing. Pir2 and splicing machinery are broadly required for gene repression. Our finding that human ARS2 also interacts with splicing factors suggests a conserved mechanism mediates gene repression through cryptic introns within lncRNAs.

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Cryptic introns in lncRNAs recruit conserved Pir2/ARS2 protein to promote gene repression [ChIP-seq]

Project description:Long non-coding RNAs (lncRNAs) dynamically regulate gene expression during development and in response to environmental conditions. In S. pombe, lncRNAs repress the expression of nearby genes via a mechanism involving silencing effector proteins. In this study, we find that invasion of a lncRNA into the neighboring gene results in inclusion of a cryptic intron that is required for its repressive activity. We show that cryptic introns are targeted by the conserved protein Pir2/ARS2 in association with splicing factors, which provide a scaffold for the recruitment of RNA degradation factors and chromatin modifying activities.

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