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PANAD/C7orf25 interacts with NXF1 to promote CDK6 mRNA nuclear export and G1/S transition

ABSTRACT: PANAD/C7orf25 interacts with NXF1 to promote CDK6 mRNA nuclear export and G1/S transition

PROVIDER: PRJNA1281543 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR34142071_1.fastq.gz	Fastqsanger.gz
	SRR34142071_2.fastq.gz	Fastqsanger.gz
	SRR34142072_1.fastq.gz	Fastqsanger.gz
	SRR34142072_2.fastq.gz	Fastqsanger.gz
	SRR34142073_1.fastq.gz	Fastqsanger.gz

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PANAD/C7orf25 interacts with NXF1 to promote CDK6 mRNA nuclear export and G1/S transition

Project description:Nuclear export factor 1 (NXF1) exerts mRNA transporter activity via binding to adaptors. We aimed to identify new NXF1 adaptors, and found that the R122/E125/G133/D139 amino acid residues of C7orf25 interacted with the Q20/K22/K23 residues in the RBD domain of NXF1, which disrupted the intramolecular interaction between the RBD and NTF2L domains of NXF1, consequently enhancing the binding of NXF1 to target mRNAs and promoting mRNA nuclear export. Furthermore, C7orf25 accelerated the G1/S transition and promoted tumor cell growth via interacting with NXF1 to promote nuclear export of CDK6 mRNA. The levels of C7orf25, NXF1, and CDK6 proteins were elevated in human hepatocellular carcinomas, and high C7orf25 levels were associated with worse survival. These findings identify C7orf25, which we named PANAD (Proliferation-Associated NXF1 Adaptor), as a novel NXF1-interacting adaptor and disclose the crucial roles of PANAD/C7orf25 in mRNA nuclear export and tumor growth, which provides potential target for cancer therapy.

2025-06-27 | GSE300612 | GEO

The mRNA export receptor NXF1 coordinates transcriptional dynamics, alternative polyadenylation and mRNA export

Project description:Alternative polyadenylation (APA) produces mRNA isoforms with different 3’UTR lengths. Previous studied indicated that 3’ end processing and mRNA nuclear export are intertwined in gene regulation. Here, we show that mRNA export factors generally facilitate usage of distal cleavage and polyadenylation sites (PASs), leading to expression of long 3’UTR isoforms. By focusing on the export receptor NXF1, which exhibits the most potent effect on APA in this study, we reveal a number of gene features that impact NXF1-dependent APA, including 3’UTR size, gene size and AT content. Surprisingly, downregulation of NXF1 results in accumulation of RNAP II at the 3’ end of genes, correlating with its role in APA regulation. Moreover, we show that NXF1 cooperates with CFI-68 to facilitate nuclear export of long 3’UTR isoform with UGUA motifs. Together, our work reveals several important roles of NXF1 in coordinating RNAPII distribution, 3’ end processing, and mRNA export of long 3’UTR transcripts, implicating NXF1 as the nexus of gene expression regulation.

2019-01-14 | GSE117701 | GEO

The mRNA export receptor NXF1 coordinates transcriptional dynamics, alternative polyadenylation and mRNA export

Project description:The mRNA export receptor NXF1 coordinates transcriptional dynamics, alternative polyadenylation and mRNA export

| PRJNA482996 | ENA

Prolonged halting of gene expression in early G1 arrest by inhibition of CDK4/CDK6 reprograms myeloma cells for cytotoxic killing

Project description:By selective and reversible inhibition of CDK4/CDK6, we have developed a strategy to both inhibit proliferation and enhance cytotoxic killing of cancer cells. Induction of prolonged early-G1 arrest (pG1) by CDK4/CDK6 inhibition halts gene expression in early-G1 and prevents expression of genes programmed for other cell cycle phases. S-phase synchronization upon removal of the early-G1 block (pG1-S) fails to completely restore scheduled gene expression. Consequently, coordinate loss of IRF4 and gain of Bim and Noxa expression sensitize myeloma tumor cells to bortezomib-induced apoptosis in pG1 and more profoundly in pG1-S in vitro. Induction of pG1 and pG1-S by CDK4/CDK6 inhibition augments tumor-specific bortezomib killing in myeloma xenografts. Inhibition of CDK4/CDK6 in combination therapy thus represents a novel mechanism-based cancer therapy. PD 0332991 (PD) is the only known specific and reversible CDK4/CDK6 inhibitor. Gene expression was measured in myeloma MM1.S cells treated with PD (0.25 uM) in triplicate for 12, 24 or 36 h, or in cells released from G1, induced by 24hPD, for 4 or 18 h.

2012-04-06 | E-GEOD-35728 | biostudies-arrayexpress

Prolonged halting of gene expression in early G1 arrest by inhibition of CDK4/CDK6 reprograms myeloma cells for cytotoxic killing

2012-04-07 | GSE35728 | GEO

Selective nuclear export of specific classes of mRNA from mammalian nuclei is promoted by GANP

Project description:The nuclear phase of the gene expression pathway culminates in the export of mature mRNAs to the cytoplasm through nuclear pore complexes (NPCs). GANP (Germinal-centre Associated Nuclear Protein) promotes the transfer to NPCs of mRNAs bound to the transport factor NXF1. Here, we demonstrate that GANP, subunit of the TREX-2 mRNA export complex, promotes selective nuclear export of a specific subset of mRNAs whose transport depends on NXF1. Genome-wide gene expression profiling showed that half of the transcripts whose nuclear export was impaired following NXF1 depletion also showed reduced export when GANP was depleted. GANP-dependent transcripts were highly expressed, yet short-lived, and were highly enriched in those encoding central components of the gene expression machinery such as RNA synthesis and processing factors. After injection into Xenopus oocyte nuclei, representative GANP-dependent transcripts showed faster nuclear export kinetics than representative transcripts that were not influenced by GANP depletion. We propose that GANP promotes the nuclear export of specific classes of mRNAs that may facilitate rapid changes in gene expression. We used gene expression profiling to compare the abundance of cytoplasmic RNAs after GANP or NXF1 depletion

2014-02-14 | E-GEOD-54481 | biostudies-arrayexpress

ChIP sequencing experiment of HA-tagged WT CDK6 or of a C-terminally truncated variant of CDK6 (CDK6 delta-C) in BCR-ABL1 expressing cell lines

Project description:The cell cycle kinase CDK6 interacts with a variety of proteins including cyclins and members of the INK4 and Cip/Kip families. These interactions are thought to involve primarily the N-lobe of the protein. Less is known about the role of the C-lobe for the function of CDK6. In this experiment we assessed the function of the C-lobe in CDK6's interaction with transcriptional complexes. We generated cell lines by retroviral over-expression of BCR-ABL1 in bone marrow cells from CDK6 knock-out mice. We then introduced HA-tagged variants of CDK6 - either wildtype CDK6 (CDK6_WT) or a C-terminally truncated variant of CDK6 lacking the last 32 amino acids of the protein (CDK6_delta-C). ChIP was performed with an antibody against the HA tag. CDK6 KO cell lines were used as controls.

2024-06-30 | E-MTAB-13798 | biostudies-arrayexpress

A heterochromatin-specific RNA export pathway facilitates piRNA production

Project description:PIWI-interacting RNAs (piRNAs) guide transposon silencing in animals. The 22-30nt piRNAs are processed in the cytoplasm from long non-coding RNAs. How piRNA precursors, which often lack RNA processing hallmarks of export-competent transcripts, achieve nuclear export is unknown. Here, we uncover the RNA export pathway specific for piRNA precursors in the Drosophila germline. This pathway requires Nxf3-Nxt1, a variant of the hetero-dimeric mRNA export receptor Nxf1-Nxt1. Nxf3 interacts with UAP56, a nuclear RNA helicase essential for mRNA export, and CG13741/Bootlegger, which recruits Nxf3-Nxt1 and UAP56 to heterochromatic piRNA source loci. Upon RNA cargo binding, Nxf3 achieves nuclear export via the exportin Crm1, and accumulates together with Bootlegger in peri-nuclear nuage, suggesting that after export, Nxf3-Bootlegger delivers precursor transcripts to the piRNA processing sites. Our findings indicate that the piRNA pathway bypasses nuclear RNA surveillance systems to achieve export of heterochromatic, unprocessed transcripts to the cytoplasm, a strategy also exploited by retroviruses.

2019-03-28 | GSE126578 | GEO

Transcriptome-wide mapping of RNA:protein interactions of seven SR proteins and NXF1 in P19 cells by iCLIP

Project description:We used GFP-tagged SR proteins expressed at endogenous levels and iCLIP to identify and compare endogenous RNA targets of individual SR proteins, map the preferential sites of binding, compare binding pattern and binding motifs between family members and to NXF1 and quantify binding of SR proteins and NXF1 to spliced versus unspliced RNAs to study the role of SR proteins in mRNA export via NXF1.

2016-03-07 | GSE69689 | GEO

Gene architecture and sequence composition underpin selective dependency of long RNAs on components of the nuclear export pathway

Project description:The nuclear export pathway transports long RNAs produced in the nucleus to the cytoplasm. The core components of this pathway are thought to be required for export of virtually all polyadenylated RNAs. Here, we depleted different proteins that act in nuclear export in human cells, and quantified the transcriptome-wide consequences on RNA localization. Different genes exhibited substantially variable sensitivities, with depletion of NXF1 and TREX components causing some transcripts to become strongly retained in the nucleus while others were not affected. Specifically, NXF1 is preferentially required for export of single- or few-exon transcripts with long exons or high A/U-content, whereas depletion of TREX complex components preferentially affects spliced and G/C-rich transcripts. Using massively parallel reporter assays we identified short sequence elements that render transcripts dependent on NXF1 for their export, and identified synergistic effects of splicing and NXF1. These results revise the current model of how nuclear export shapes the distribution of RNA within human cells.

2020-05-25 | GSE139151 | GEO

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