The mRNA export receptor NXF1 coordinates transcriptional dynamics, alternative polyadenylation and mRNA export
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PROVIDER: PRJNA482996 | ENA |
REPOSITORIES: ENA
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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
Project description: Not available
| S-EPMC6450743 | biostudies-literature
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
Project description:The yeast mRNA export adaptor Yra1 binds the Pcf11 subunit of cleavage-polyadenylation factor CF1A linking export to 3'-end formation. We found a surprising consequence of this interaction is that Yra1 influences cleavage-polyadenylation. Yra1 competes with the CF1A subunit, Clp1, for binding to Pcf11, and excess Yra1 inhibits 3' processing in vitro. Release of Yra1 at the 3' ends of genes coincides with recruitment of Clp1, and depletion of Yra1 enhances Clp1 recruitment within some genes. These results suggest that CF1A is not necessarily recruited as a complete unit, but instead Clp1 can be incorporated co-transcriptionally in a process regulated by Yra1. Yra1 depletion causes widespread changes in poly(A) site choice particularly at sites where the efficiency element is divergently positioned. We propose that one way Yra1 modulates cleavage-polyadenylation is by influencing co-transcriptional assembly of the CF1A/B 3' processing factor. Key Words: Yra1, cleavage-polyadenylation, mRNA export, Pcf11, Clp1, Sub2, alternative polyadenylation Whole genome analysis of Yra1, Sub2, Pcf11, and Clp1 in WT and Yra1-depleted cells using a GAL1-YRA1 mutant. ChiP-ChIP using ligation-mediated PCR amplified material hybridized to Nimblegen 385K arrays 50mers median probe spacing 32 bp cat. No. C4214-00-01.
2011-09-24 | E-GEOD-30705 | biostudies-arrayexpress
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.
2014-02-14 | GSE54481 | GEO
Project description:The yeast mRNA export adaptor Yra1 binds the Pcf11 subunit of cleavage-polyadenylation factor CF1A linking export to 3'-end formation. We found a surprising consequence of this interaction is that Yra1 influences cleavage-polyadenylation. Yra1 competes with the CF1A subunit, Clp1, for binding to Pcf11, and excess Yra1 inhibits 3' processing in vitro. Release of Yra1 at the 3' ends of genes coincides with recruitment of Clp1, and depletion of Yra1 enhances Clp1 recruitment within some genes. These results suggest that CF1A is not necessarily recruited as a complete unit, but instead Clp1 can be incorporated co-transcriptionally in a process regulated by Yra1. Yra1 depletion causes widespread changes in poly(A) site choice particularly at sites where the efficiency element is divergently positioned. We propose that one way Yra1 modulates cleavage-polyadenylation is by influencing co-transcriptional assembly of the CF1A/B 3' processing factor. Key Words: Yra1, cleavage-polyadenylation, mRNA export, Pcf11, Clp1, Sub2, alternative polyadenylation
2011-09-25 | GSE30705 | GEO
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
Project description:PGC-1α plays a central role in maintaining mitochondrial and energy metabolism homeostasis, linking external stimuli to transcriptional co-activation of genes involved in adaptive and age-related pathways. The carboxyl-terminus encodes a serine/arginine-rich (RS) region and a putative RNA recognition motif, however the potential RNA-processing function(s) remained elusive for the past 20 years. Here, we show that the RS domain of human PGC-1α directly interacts with RNA and the nuclear RNA export receptor NXF1. Inducible depletion of PGC-1α and expression of RNAi-resistant RS-deleted PGC-1α further demonstrated that its RNA/NXF1-binding activity is required for the nuclear exportof a subset of mRNAsand mitochondrial homeostasis.Genome-wide investigations revealed that the nuclear export function is not strictly linked to PGC-1α-binding promoters, identifyingin turnnovel mRNA nuclear export targets inmRNA- and age-related pathways.These findingsprovide new directions to further elucidate the roles of PGC-1α in gene expression, metabolic disorders, ageing andneurodegeneration.
2023-07-19 | GSE230413 | GEO
Project description:PGC-1α plays a central role in maintaining mitochondrial and energy metabolism homeostasis, linking external stimuli to transcriptional co-activation of genes involved in adaptive and age-related pathways. The carboxyl-terminus encodes a serine/arginine-rich (RS) region and a putative RNA recognition motif, however the potential RNA-processing function(s) remained elusive for the past 20 years. Here, we show that the RS domain of human PGC-1α directly interacts with RNA and the nuclear RNA export receptor NXF1. Inducible depletion of PGC-1α and expression of RNAi-resistant RS-deleted PGC-1α further demonstrated that its RNA/NXF1-binding activity is required for the nuclear exportof a subset of mRNAsand mitochondrial homeostasis.Genome-wide investigations revealed that the nuclear export function is not strictly linked to PGC-1α-binding promoters, identifyingin turnnovel mRNA nuclear export targets inmRNA- and age-related pathways.These findingsprovide new directions to further elucidate the roles of PGC-1α in gene expression, metabolic disorders, ageing andneurodegeneration.
2023-07-19 | GSE230428 | GEO
Project description:5-methylcytosine promotes mRNA export
| PRJNA362296 | ENA