Nuclear export of circular RNA
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA941274 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23714354.fastq.gz | Fastqsanger.gz | |||
| SRR23714355.fastq.gz | Fastqsanger.gz | |||
| SRR23714356.fastq.gz | Fastqsanger.gz |
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Project description:Nuclear export of circular RNA
| PRJNA988001 | ENA
Project description:Circular RNAs (circRNAs), which can function as regulators of gene expression, are formed by back-splicing of precursor mRNAs in the nucleus. circRNAs are predominantly localized in the cytoplasm, indicating that they must be exported from the nucleus. Here, we uncover a pathway specific for nuclear export of circular RNA. This pathway requires Ran-GTP, Exportin-2 and IGF2BP1. Enhancing the nuclear Ran-GTP gradient by depletion or chemical inhibition of the major protein exporter, CRM1, selectively increases nuclear export of circRNAs, while reducing the nuclear Ran-GTP gradient selectively blocks circRNA export. Analysis of nuclear circRNA binding proteins reveals that interaction of IGF2BP1 with circRNA is enhanced by Ran-GTP, whereas its interaction with linear RNA is inhibited by Ran-GTP. Depletion or knockout of Exportin-2 specifically inhibits nuclear export of circRNA, while formation of an Exportin-2 circRNA export complex requires Ran-GTP and IGF2BP1. Our findings demonstrate that adaptors such as IGF2BP1 that bind directly to circular RNAs recruit Exportin-2 to export circRNAs in a mechanism analogous to protein export, rather than mRNA export.
2023-12-09 | GSE235899 | GEO
Project description:Circular RNAs (circRNAs), which are increasingly being implicated in a variety of functions in normal and cancerous cells1-5, are formed by back-splicing of precursor mRNAs in the nucleus6-10. circRNAs are predom¬inantly localized in the cytoplasm, indicating that they must be exported from the nucleus. Here, we uncover a pathway specific for nuclear export of circular RNA. This pathway requires Ran-GTP, Exportin-2 and IGF2BP1. Enhancing the nuclear Ran-GTP gradient by depletion or chemical inhibition of the major protein exporter, CRM1, selectively increases nuclear export of circRNAs, while reducing the nuclear Ran-GTP gradient selectively blocks circRNA export. Depletion or knockout of Exportin-2 specifically inhibits nuclear export of circRNA. Analysis of nuclear circRNA binding proteins reveals that interaction of IGF2BP1 with circRNA is enhanced by Ran-GTP. Formation of circRNA export complexes in the nucleus is promoted by Ran-GTP through its interactions with IGF2BP1, Exportin-2 and circRNA. Our findings demonstrate that adaptors such as IGF2BP1 that bind directly to circular RNAs recruit Ran-GTP and Exportin-2 to export circRNAs in a mechanism analogous to protein export, rather than mRNA export.
2023-11-22 | GSE226716 | GEO
Project description:Altered RNA export by SF3B1 mutants confers sensitivity to nuclear export inhibition
| PRJNA1073893 | ENA
Project description:N6-methyladenosine-Mediated Nuclear Export of Messenger RNA
| PRJNA300279 | ENA
Project description:Small RNA silencing pathways protect genome integrity in part through establishing heterochromatin at transposon loci. In animals, this process requires piRNA-guided targeting of nuclear PIWI proteins to nascent transcripts. The molecular events contributing to heterochromatin formation upon PIWI binding to nascent RNA, a transient molecule at chromatin, are unknown. Here, we identify SFINX, a protein complex that is required for Piwi-mediated co-transcriptional silencing in Drosophila. It consists of Nxf2—a variant of the nuclear RNA export factor Nxf1/Tap, the mRNA export co-factor Nxt1/p15, and the Piwi-associated protein Panoramix. In the absence of Nxf2, Panoramix is targeted for degradation and piRNA-loaded Piwi is unable to establish heterochromatin. Consequently, nxf2 mutants exhibit severe transposon de-repression and are sterile. We show that within SFINX, Panoramix connects to the heterochromatin machinery while Nxf2 enables target silencing via nascent RNA. Thus, the Nxf2-Nxt1 heterodimer—despite having originated from core mRNA export machinery—has been repurposed for heterochromatin formation. Our data establish an unexpected link between nuclear small RNA biology and NXF-variants, which are widespread in animal lineages, but mostly lack ascribed functions.
2019-06-12 | PXD011201 | Pride
Project description:Nuclear export of mRNA is essential for eukaryotic cells to establish the flow of genetic information in the nucleus to protein synthesis in the cytoplasm. This transport process is highly regulated to ensure efficient and accurate gene expression. Viruses are well known for their ability to manipulate host gene expression. Here, we report that ORF10 of Kaposi’s sarcoma associated herpesvirus (KSHV), a nuclear DNA virus, inhibits mRNA export in a transcript-selective manner to control cellular gene expression. This export inhibitory effect of ORF10 requires the interaction with an RNA export factor, Rae1. Genome-wide analysis by RNA sequencing revealed the subset of cellular mRNAs whose nuclear export is blocked by ORF10. The 3’ untranslated regions (3’ UTRs) of ORF10-targeted transcripts confer their sensitivity to nuclear export inhibition by ORF10. In the context of KSHV replication, the interaction of ORF10 with Rae1 is important for the virus to express viral genes and produce infectious virions. Our results suggest that a nuclear replicating DNA virus can selectively interfere with RNA export through Rae1 to restrict host gene expression for optimal viral replication.
2016-10-18 | GSE82241 | GEO
Project description:The eukaryotic mRNA life cycle includes transcription, nuclear mRNA export and degradation. To quantify all these processes simultaneously, we perform thiol-linked alkylation after metabolic labeling of RNA with 4-thiouridine (4sU), followed by sequencing of RNA (SLAM-seq) in the nuclear and cytosolic compartments. We develop a model that reliably quantifies mRNA synthesis, nuclear export, and nuclear and cytosolic degradation rates on a genome-wide scale. We find that nuclear degradation of polyadenylated mRNA is negligible and nuclear mRNA export is slow, while cytosolic mRNA degradation is comparatively fast. Consequently, an mRNA molecule generally spends most of its life in the nucleus. We also observe large differences in the nuclear export rates of different 3’UTR transcript isoforms. Furthermore, we identify genes whose expression is abruptly induced upon metabolic labeling. These transcripts are exported substantially faster than average mRNAs, suggesting the existence of alternative export pathways. Our results highlight nuclear mRNA export as a limiting factor in mRNA metabolism and gene regulation.
2024-04-23 | GSE233546 | GEO
Project description:Genomes are promiscuously transcribed, necessitating mechanisms that facilitate the sorting of RNA for function or destruction. The polyA (pA) tail is one such distinguishing feature, which in the S. cerevisiae nucleus is bound by the Nab2p protein, yielding transcript protection. As Nab2p also contacts the main nuclear export factor Mex67p, we asked whether transport kinetics contributes to RNA sorting. Indeed, 3’end sequencing of newly transcribed pA+ RNAs demonstrates that nuclear depletion of Mex67p elicits their instant and global decay. A similar phenotype is evident upon inactivation of other export factors and proportional to the amount of nuclear pA+ RNA. Since RNA production is partially rescued by Nab2p over-expression, we propose that an export-block out-titrates Nab2p onto nuclear retained pA+ RNA, reducing the pool of Nab2p free to protect new transcripts. More generally, we suggest that nuclear RNA decay, negotiated by Nab2p availability, aids in balancing cellular transcript supply with demand.
2018-08-28 | GSE108477 | GEO
Project description:SF3B1 mutations are the most frequent spliceosomal alterations across cancers, yet no successful therapy exists to target this pathway. Previous findings from a phase 2 clinical trial of the XPO1 inhibitor selinexor in patients with high-risk myelodysplastic neoplasms (MDS) relapsed or refractory to hypomethylating agents (HMA) revealed increased activity in patients with SF3B1 mutations. XPO1 (Exportin-1) is responsible for the export of over 200 proteins, but also plays a role in the transport of multiple RNA species, including small nuclear RNAs (snRNAs), ribosomal RNAs (rRNAs), and select messenger RNAs (mRNAs) out of the nucleus. We therefore hypothesized that XPO1 inhibition perturbs RNA export and may preferentially affect SF3B1 mutants via altered splicing, given the role of XPO1 in exporting snRNAs, which form the catalytic portion of the spliceosome. To evaluate the mechanism underlying preferentially sensitivity of SF3B1-mutants to XPO1 inhibition, we performed nuclear and cytoplasmic fraction followed by RNA sequencing before and after XPO1 inhibition in SF3B1 wildtype and SF3B1 K666N cells (subcellular RNA-seq). Whole transcriptomic analysis of subcellular RNA-seq data revealed more nuclear retention of global RNA transcripts after XPO1 inhibition in the SF3B1 mutant cell line. Similarly, we performed subcellular RNA-seq for small RNAs and found snRNAs to be increased in the nucleus after XPO1 inhibition in the SF3B1 mutant cells. We then performed total cellular RNA sequencing to understand the effect of XPO1 inhibition on global RNA expression and RNA splicing. Differential gene expression analysis identified that XPO1 inhibition had the greatest effect on cell cycle in SF3B1 wildtype cells but in SF3B1-mutant cells differentiation pathways were more significantly affected. Alternative splicing analysis showed increased 3’ alternative splicing events in SF3B1 mutant after XPO1 inhibition. These results signify the mechanistic basis for preferential sensitivity of SF3B1 mutant cells to nuclear export inhibition arises through nuclear retention of spliceosomal snRNAs and select mRNAs that result in perturbation of differentiation pathways.
2024-08-05 | GSE255179 | GEO