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mRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcription.

GSE183569 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2025/02/13 Platform GPL18573
Summary
Several transcription inhibitors have been developed as cancer therapies. However, they show modest clinical activity highlighting that our understanding of the cellular response to transcriptional inhibition remains incomplete. Here we report that potent inhibitors of transcription not only impact mRNA output, but also markedly impair mRNA transcript localisation and nuclear export. We demonstrate that retention of newly transcribed mRNA in nuclear speckles is an adaptive response to chemically distinct transcriptional inhibitors. Retained transcripts are fully processed and accumulate in proportion to the expression level of the genes from which they emanate. The TREX mRNA export complex plays an integral role in directing nascent transcripts to nuclear speckles where they are bound to NXF1, protected from degradation, and poised for rapid export following re-initiation of transcription. Our findings provide new insights into the crosstalk between transcription and mRNA export, with important implications for drugs aiming to inhibit transcription for therapeutic gain.
Published in
mRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcription
Williams TD, Michalak EM, Carey KT et al. · Molecular cell 2025 · PMID 39753105 · doi:10.1016/j.molcel.2024.12.008
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Also filed as BioProject PRJNA761338 and SRA study SRP335987. Searching any of these in the dataset finder brings you back here.

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