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Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA is driven by intron retention

ABSTRACT: Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA is driven by intron retention

PROVIDER: PRJNA717785 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14083439_1.fastq.gz	Fastqsanger.gz
	SRR14083439_2.fastq.gz	Fastqsanger.gz
	SRR14083440_1.fastq.gz	Fastqsanger.gz
	SRR14083440_2.fastq.gz	Fastqsanger.gz
	SRR14083441_1.fastq.gz	Fastqsanger.gz

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Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA is driven by intron retention.

Project description:The spatial partitioning of the transcriptome in the cell is an important form of gene-expression regulation. Here, we address how intron retention influences the spatio-temporal dynamics of transcripts from two clinically relevant genes: TERT (Telomerase Reverse Transcriptase) pre-mRNA and TUG1 (Taurine-Upregulated Gene 1) lncRNA. Single molecule RNA FISH reveals that nuclear TERT transcripts uniformly and robustly retain specific introns. Our data suggest that the splicing of TERT retained introns occurs during mitosis. In contrast, TUG1 has a bimodal distribution of fully spliced cytoplasmic and intron-retained nuclear transcripts. We further test the functionality of intron-retention events using RNA-targeting thiomorpholino antisense oligonucleotides to block intron excision. We show that intron retention is the driving force for the nuclear compartmentalization of these RNAs. For both RNAs, altering this splicing-driven subcellular distribution has significant effects on cell viability. Together, these findings show that stable retention of specific introns can orchestrate spatial compartmentalization of these RNAs within the cell. This process reveals that modulating RNA localization via targeted intron retention can be utilized for RNA-based therapies.

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Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA is driven by intron retention

Project description:We performed poly(A) enriched RNA sequencing of HeLa, U-2 OS and mES cells. This series includes two re-analyzed samples from mouse: GSM1032506 and GSM1032518 (denoted as iPS.A and iPS.B, respectively). The re-analyzed data for these samples are included in the file INCLUSION_LEVELS_FULL-Mm25.tab.gz. This series includes three re-analyzed samples from human: GSM808734, GSM1023087 and GSM1023070 (denoted as iPS.A, iPS.B and iPS.C, respectively). The re-analyzed data for these samples are included in the file INCLUSION_LEVELS_FULL-Hs23.tab.gz

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Project description:We present an analysis of intron retention under stress from two different drugs and their combinations in yeast Saccharomyces cerevisiae. We previously established isogrowth profiling, a method to abstract the non-specific effects of growth rate inhibition from the specific effect of perturbation by a small molecule: two drugs are used at varied ratios, but at fixed overall growth inhibition. Here, cycloheximide and LiCl were used at seven different ratios along the 50% growth inhibition isobole and the total ribodepleted RNA was sequenced. This allowed us to gauge the changes in intron retention due to the used drugs, while ensuring that the effects are not caused by growth inhibition. We found a prominent increase in intron retention under LiCl treatment that preferentially affects introns contained in the transcripts of ribosomal proteins.

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