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

ABSTRACT: 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

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE169743 | GEO | 2021/03/27

REPOSITORIES: GEO

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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.

| S-EPMC8175569 | biostudies-literature

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