Conserved protein Pir2ARS2 mediates gene repression through cryptic introns in lncRNAs
| Autor: | Jothy Dhakshnamoorthy, Sahana Holla, Hua Xiao, Gobi Thillainadesan, David C. Wheeler, Lisa M. Miller Jenkins, Shiv I. S. Grewal |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Genetics Multidisciplinary biology Science Intron General Physics and Astronomy General Chemistry biology.organism_classification General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Schizosaccharomyces pombe RNA splicing Gene expression Gene silencing lcsh:Q Epigenetics lcsh:Science Gene Psychological repression 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-11 (2020) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-16280-y |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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