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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE183571 | GEO | 2025/02/12

REPOSITORIES: GEO

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

Project description: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.

2025-02-13 | GSE183570 | GEO

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

2025-02-13 | GSE183569 | GEO

mRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcription [SLAM-seq]

2025-02-13 | GSE284174 | GEO

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

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

| PRJNA761339 | ENA

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

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

| PRJNA761329 | ENA

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

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

| PRJNA761338 | ENA

mRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcription [SLAM-seq]

Project description:mRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcription [SLAM-seq]

| PRJNA1197500 | ENA

Intronless mRNAs transit through nuclear speckles to gain export competence.

Project description:Nuclear speckles (NSs) serve as splicing factor storage sites. In this study, we unexpectedly found that many endogenous intronless mRNAs, which do not undergo splicing, associate with NSs. These associations do not require transcription, polyadenylation, or the polyA tail. Rather, exonic splicing enhancers present in intronless mRNAs and their binding partners, SR proteins, promote intronless mRNA localization to NSs. Significantly, speckle targeting of mRNAs promotes the recruitment of the TREX export complex and their TREX-dependent nuclear export. Furthermore, TREX, which accumulates in NSs, is required for releasing intronless mRNAs from NSs, whereas NXF1, which is mainly detected at nuclear pores, is not. Upon NXF1 depletion, the TREX protein UAP56 loses speckle concentration but coaccumulates with intronless mRNAs and polyA RNAs in the nucleoplasm, and these RNAs are trapped in NSs upon UAP56 codepletion. We propose that the export-competent messenger RNP assembly mainly occurs in NSs for intronless mRNAs and that entering NSs serves as a quality control step in mRNA export.

| S-EPMC6219727 | biostudies-literature

mRNAs are sorted for export or degradation before passing through nuclear speckles.

Project description:A significant fraction of mRNAs are degraded by the nuclear exosome in normal cells. Here, we studied where and when these exosome target mRNAs are sorted away from properly exported ones in the cells. We show that upon exosome inactivation, polyA RNAs are apparently accumulated in nuclear foci that are distinct from nuclear speckles (NSs), and provide several lines of evidence supporting that these polyA RNAs mainly correspond to accumulating exosome target mRNAs. These results suggest that exosomal mRNA degradation mostly occurs outside of NSs. In support of this possibility, targeting exosome target mRNAs to NSs stabilizes them by preventing exosomal degradation. Furthermore, inhibiting mRNA release from NSs does not attenuate exosomal degradation in normal cells, and results in polyA RNA accumulation both inside and outside of NSs in exosome inactivated cells, suggesting that passage through NSs is not required for sorting mRNAs for degradation or export. Indeed, exosome target mRNAs that normally do not enter NSs are exported upon exosome inactivation. Together, our data suggest that exosome target mRNAs are mainly degraded in the nucleoplasm before entering NSs and rapid removal of these mRNAs is important for preventing their nuclear export.

| S-EPMC6144872 | biostudies-literature

Herpesviral replication compartments move and coalesce at nuclear speckles to enhance export of viral late mRNA.

Project description:The role of the intranuclear movement of chromatin in gene expression is not well-understood. Herpes simplex virus forms replication compartments (RCs) in infected cell nuclei as sites of viral DNA replication and late gene transcription. These structures develop from small compartments that grow in size, move, and coalesce. Quantitative analysis of RC trajectories, derived from 4D images, shows that most RCs move by directed motion. Directed movement is impaired in the presence of actin and myosin inhibitors as well as a transcription inhibitor. In addition, RCs coalesce at and reorganize nuclear speckles. Lastly, distinct effects of actin and myosin inhibitors on viral gene expression suggest that RC movement is not required for transcription, but rather, movement results in the bridging of transcriptionally active RCs with nuclear speckles to form structures that enhance export of viral late mRNAs.

| S-EPMC3102408 | biostudies-literature

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