Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA is driven by intron retention.
Animals
Cell Compartmentation
Cell Line
Cell Line, Tumor
Cell Nucleus
/ genetics
HCT116 Cells
HEK293 Cells
HeLa Cells
Human Embryonic Stem Cells
/ cytology
Humans
In Situ Hybridization, Fluorescence
Induced Pluripotent Stem Cells
/ cytology
Introns
Mice
Mitosis
RNA Precursors
/ genetics
RNA Splicing
RNA Stability
RNA, Long Noncoding
/ genetics
RNA, Messenger
/ genetics
Species Specificity
Telomerase
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 06 2021
03 06 2021
Historique:
received:
10
07
2020
accepted:
07
04
2021
entrez:
4
6
2021
pubmed:
5
6
2021
medline:
12
6
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34083519
doi: 10.1038/s41467-021-23221-w
pii: 10.1038/s41467-021-23221-w
pmc: PMC8175569
doi:
Substances chimiques
RNA Precursors
0
RNA, Long Noncoding
0
RNA, Messenger
0
TUG1 long noncoding RNA, human
0
TERT protein, human
EC 2.7.7.49
Telomerase
EC 2.7.7.49
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3308Subventions
Organisme : NIGMS NIH HHS
ID : P01 GM099117
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : CIHR
Pays : Canada
Commentaires et corrections
Type : ErratumIn
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