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Reference - PMID:32415063 - Conserved protein Pir2 ARS2 mediates gene repression through cryptic introns in lncRNAs.

Reference summary

PubMed ID
PMID:32415063
Title
Conserved protein Pir2 ARS2 mediates gene repression through cryptic introns in lncRNAs.
Authors
Thillainadesan G, Xiao H, Holla S, Dhakshnamoorthy J, Jenkins LMM, Wheeler D, Grewal SIS
Citation
Nat Commun 2020 May 15;11(1):2412
Publication year
2020
Abstract
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 Pir2 ARS2 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.

Annotation

GO biological process

GO:0031047 - regulatory ncRNA-mediated gene silencing

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GO cellular component

GO:0000785 - chromatin

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GO molecular function

GO:0106222 - lncRNA binding

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Multi-locus phenotype

FYPO:0006548 - increased gene expression

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FYPO:0002052 - normal sporulation frequency

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FYPO:0006076 - siRNA absent from cell

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Single locus phenotype

FYPO:0008155 - abnormal regulatory lncRNA 3'-end processing

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FYPO:0000121 - abnormal sporulation

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FYPO:0001678 - abolished protein localization to chromatin

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FYPO:0006631 - decreased protein localization to chromatin

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FYPO:0001645 - decreased protein-protein interaction

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Genotypes:

FYPO:0006548 - increased gene expression

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