Gene expression amplification by nuclear speckle association
| Autor: | Gabriela Andrea Hernandez Gonzalez, Nimish Khanna, Jiah Kim, Andrew S. Belmont, Neha Chivukula Venkata |
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| Rok vydání: | 2019 |
| Předmět: |
Transcriptional Activation
Transcription Genetic RNA Splicing Transgene Intranuclear Inclusion Bodies Gene Expression RNA polymerase II CHO Cells HSPA1B Cricetulus Transcription (biology) Report Gene expression Animals Humans HSP70 Heat-Shock Proteins RNA Messenger Gene Research Articles Cell Nucleus Messenger RNA biology Gene Amplification Nuclear Proteins RNA Cell Biology Molecular biology biology.protein RNA Polymerase II Heat-Shock Response |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.201904046 |
| Popis: | Many active genes position near nuclear speckles. Kim et al. show that Hsp70 speckle association correlates with increased nascent transcripts. Live-cell imaging shows that increases in nascent Hsp70 transcripts strictly follow speckle association (∼0–2 min), suggesting that speckle association amplifies gene expression. Many active genes reproducibly position near nuclear speckles, but the functional significance of this positioning is unknown. Here we show that HSPA1B BAC transgenes and endogenous Hsp70 genes turn on 2–4 min after heat shock (HS), irrespective of their distance to speckles. However, both total HSPA1B mRNA counts and nascent transcript levels measured adjacent to the transgene are approximately twofold higher for speckle-associated alleles 15 min after HS. Nascent transcript level fold-increases for speckle-associated alleles are 12–56-fold and 3–7-fold higher 1–2 h after HS for HSPA1B transgenes and endogenous genes, respectively. Severalfold higher nascent transcript levels for several Hsp70 flanking genes also correlate with speckle association at 37°C. Live-cell imaging reveals that HSPA1B nascent transcript levels increase/decrease with speckle association/disassociation. Initial investigation reveals that increased nascent transcript levels accompanying speckle association correlate with reduced exosome RNA degradation and larger Ser2p CTD-modified RNA polymerase II foci. Our results demonstrate stochastic gene expression dependent on positioning relative to a liquid-droplet nuclear compartment through “gene expression amplification.” |
| Databáze: | OpenAIRE |
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