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

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Gabrijela Dumbović ◽  
Ulrich Braunschweig ◽  
Heera K. Langner ◽  
Michael Smallegan ◽  
Josep Biayna ◽  
...  
Keyword(s):  
Single Molecule ◽  
Gene Expression Regulation ◽  
Temporal Dynamics ◽  
Intron Retention ◽  
Bimodal Distribution ◽  
Spatial Partitioning ◽  
Rna Targeting ◽  
Spatio Temporal ◽  
Retained Introns ◽  
Nuclear Compartmentalization

AbstractThe 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.

scholarly journals Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA transcripts is driven by intron retention: implications for RNA-directed therapies

2020 ◽  
Author(s):  
Gabrijela Dumbović ◽  
Ulrich Braunschweig ◽  
Heera K. Langner ◽  
Katarzyna Jastrzebska ◽  
Michael Smallegan ◽  
...  
Keyword(s):  
Single Molecule ◽  
Temporal Dynamics ◽  
Intron Retention ◽  
Single Cells ◽  
Bimodal Distribution ◽  
Protein Coding ◽  
Rna Molecules ◽  
Global Connections ◽  
Spatio Temporal ◽  
Nuclear Compartmentalization

AbstractNumerous global connections have been made between splicing and other layers of gene regulation, including the spatial partitioning of the transcriptome in the cell. Yet, there has been surprisingly little analysis of the spatio-temporal regulation of individual protein-coding and non-coding RNA molecules in single cells. 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 revealed that nuclear TERT transcripts uniformly and robustly retain two specific introns whose splicing 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 had significant effects on cell growth. Together, these findings show that stable retention of specific introns can orchestrate spatial compartmentalization of RNAs within the cell; this process reveals new targets for RNA-based therapies.

scholarly journals Single molecule tracking reveals spatio-temporal dynamics of bacterial DNA repair centres

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Thomas C. Rösch ◽  
Stephan Altenburger ◽  
Luis Oviedo-Bocanegra ◽  
Miriam Pediaditakis ◽  
Nina El Najjar ◽  
...  
Keyword(s):  
Dna Repair ◽  
Single Molecule ◽  
Temporal Dynamics ◽  
Single Molecule Tracking ◽  
Bacterial Dna ◽  
Spatio Temporal

Spatial and temporal dynamics of Pacific capelin Mallotus catervarius in the Gulf of Alaska: implications for ecosystem-based fisheries management

2020 ◽  
Vol 637 ◽  
pp. 117-140 ◽  
Author(s):  
DW McGowan ◽  
ED Goldstein ◽  
ML Arimitsu ◽  
AL Deary ◽  
O Ormseth ◽  
...  
Keyword(s):  
Temporal Dynamics ◽  
Marine Ecosystem ◽  
Gulf Of Alaska ◽  
Data Series ◽  
Limited Information ◽  
Important Species ◽  
Multiple Data ◽  
Spatial And Temporal Dynamics ◽  
Spawning Areas ◽  
Spatio Temporal

Pacific capelin Mallotus catervarius are planktivorous small pelagic fish that serve an intermediate trophic role in marine food webs. Due to the lack of a directed fishery or monitoring of capelin in the Northeast Pacific, limited information is available on their distribution and abundance, and how spatio-temporal fluctuations in capelin density affect their availability as prey. To provide information on life history, spatial patterns, and population dynamics of capelin in the Gulf of Alaska (GOA), we modeled distributions of spawning habitat and larval dispersal, and synthesized spatially indexed data from multiple independent sources from 1996 to 2016. Potential capelin spawning areas were broadly distributed across the GOA. Models of larval drift show the GOA’s advective circulation patterns disperse capelin larvae over the continental shelf and upper slope, indicating potential connections between spawning areas and observed offshore distributions that are influenced by the location and timing of spawning. Spatial overlap in composite distributions of larval and age-1+ fish was used to identify core areas where capelin consistently occur and concentrate. Capelin primarily occupy shelf waters near the Kodiak Archipelago, and are patchily distributed across the GOA shelf and inshore waters. Interannual variations in abundance along with spatio-temporal differences in density indicate that the availability of capelin to predators and monitoring surveys is highly variable in the GOA. We demonstrate that the limitations of individual data series can be compensated for by integrating multiple data sources to monitor fluctuations in distributions and abundance trends of an ecologically important species across a large marine ecosystem.

Spatio‐temporal dynamics of water quality and eutrophication in Lake Taihu, China

Ecohydrology ◽  
2021 ◽  
Author(s):  
Qiongfang Li ◽  
Yuting Zhu ◽  
Qihui Chen ◽  
Yu Li ◽  
Jing Chen ◽  
...  
Keyword(s):  
Water Quality ◽  
Temporal Dynamics ◽  
Lake Taihu ◽  
Spatio Temporal

scholarly journals Simultaneous spatiotemporal super-resolution and multi-parametric fluorescence microscopy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jagadish Sankaran ◽  
Harikrushnan Balasubramanian ◽  
Wai Hoh Tang ◽  
Xue Wen Ng ◽  
Adrian Röllin ◽  
...  
Keyword(s):  
Single Molecule ◽  
Temporal Dynamics ◽  
Growth Factor Receptor ◽  
Super Resolution ◽  
Actin Binding ◽  
Biological Knowledge ◽  
Data Set ◽  
Epidermal Growth ◽  
Molecular Brightness ◽  
Super Resolution Microscopy

AbstractSuper-resolution microscopy and single molecule fluorescence spectroscopy require mutually exclusive experimental strategies optimizing either temporal or spatial resolution. To achieve both, we implement a GPU-supported, camera-based measurement strategy that highly resolves spatial structures (~100 nm), temporal dynamics (~2 ms), and molecular brightness from the exact same data set. Simultaneous super-resolution of spatial and temporal details leads to an improved precision in estimating the diffusion coefficient of the actin binding polypeptide Lifeact and corrects structural artefacts. Multi-parametric analysis of epidermal growth factor receptor (EGFR) and Lifeact suggests that the domain partitioning of EGFR is primarily determined by EGFR-membrane interactions, possibly sub-resolution clustering and inter-EGFR interactions but is largely independent of EGFR-actin interactions. These results demonstrate that pixel-wise cross-correlation of parameters obtained from different techniques on the same data set enables robust physicochemical parameter estimation and provides biological knowledge that cannot be obtained from sequential measurements.

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