RBBP6 anchors pre-mRNA 3’ end processing to nuclear speckles for efficient gene expression
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ABSTRACT:
PROVIDER: PRJNA1082279 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28165100.fastq.gz | Fastqsanger.gz | |||
| SRR28165101.fastq.gz | Fastqsanger.gz | |||
| SRR28165102.fastq.gz | Fastqsanger.gz | |||
| SRR28165103_1.fastq.gz | Fastqsanger.gz | |||
| SRR28165103_2.fastq.gz | Fastqsanger.gz |
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Project description:Pre-mRNA 3′ processing is an integral step in mRNA biogenesis. However, where this process occurs in the nucleus remains unknown. Here, we demonstrate that nuclear speckles (NSs), membraneless organelles enriched with splicing factors, are major sites for pre-mRNA 3′ processing in human cells. We show that the essential pre-mRNA 3′ processing factor RBBP6 associates strongly with NSs via its C-terminal intrinsically disordered region (IDR). Importantly, although the conserved N-terminal domain (NTD) of RBBP6 is sufficient for pre-mRNA 3′ processing in vitro, its IDR-mediated association with NSs is required for efficient pre-mRNA 3′ processing in cells. Through proximity labeling analyses, we provide evidence that pre-mRNA 3′ processing for over 50% of genes occurs near NSs. We propose that NSs serve as hubs for RNA polymerase II transcription, pre-mRNA splicing, and 3′ processing, thereby enhancing the efficiency and coordination of different gene expression steps.
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Project description:Nuclear Speckles are large, multi-component condensates in the mammalian nuclei that are thought to be involved in various stages of gene expression, including transcription, splicing, and export. Investigating the direct role of Speckles in these processes have been intractable due to their heterogeneous, multi-component nature. Here we show that Speckles are necessary for the splicing of GC-rich, levelled intron/exon architecture. Acute removal of Speckles leads to a drastic downregulation of GC-rich genes which are clustered within GC-rich isochores. Genes outside these domains are physically away from Speckles and are not affected from loss of Speckles. Animal genomes that do not have GC-rich isochores, do not have GC-rich levelled intron/exon architecture and do not have Speckles. Our results suggest that the expansion of Speckles core proteins’ intrinsically disordered domains during vertebrate evolution facilitated GC-content elevation in Amniotes by creating a condensate necessary to splice the by-products of this process: GC-rich, levelled intron/exon architecture.
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Project description:Nuclear Speckles are large, multi-component condensates in the mammalian nuclei that are thought to be involved in various stages of gene expression, including transcription, splicing, and export. Investigating the direct role of Speckles in these processes have been intractable due to their heterogeneous, multi-component nature. Here we show that Speckles are necessary for the splicing of GC-rich, levelled intron/exon architecture. Acute removal of Speckles leads to a drastic downregulation of GC-rich genes which are clustered within GC-rich isochores. Genes outside these domains are physically away from Speckles and are not affected from loss of Speckles. Animal genomes that do not have GC-rich isochores, do not have GC-rich levelled intron/exon architecture and do not have Speckles. Our results suggest that the expansion of Speckles core proteins’ intrinsically disordered domains during vertebrate evolution facilitated GC-content elevation in Amniotes by creating a condensate necessary to splice the by-products of this process: GC-rich, levelled intron/exon architecture.
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Project description:Nuclear Speckles are large, multi-component condensates in the mammalian nuclei that are thought to be involved in various stages of gene expression, including transcription, splicing, and export. Investigating the direct role of Speckles in these processes have been intractable due to their heterogeneous, multi-component nature. Here we show that Speckles are necessary for the splicing of GC-rich, levelled intron/exon architecture. Acute removal of Speckles leads to a drastic downregulation of GC-rich genes which are clustered within GC-rich isochores. Genes outside these domains are physically away from Speckles and are not affected from loss of Speckles. Animal genomes that do not have GC-rich isochores, do not have GC-rich levelled intron/exon architecture and do not have Speckles. Our results suggest that the expansion of Speckles core proteins’ intrinsically disordered domains during vertebrate evolution facilitated GC-content elevation in Amniotes by creating a condensate necessary to splice the by-products of this process: GC-rich, levelled intron/exon architecture.
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Project description:Nuclear Speckles are large, multi-component condensates in the mammalian nuclei that are thought to be involved in various stages of gene expression, including transcription, splicing, and export. Investigating the direct role of Speckles in these processes have been intractable due to their heterogeneous, multi-component nature. Here we show that Speckles are necessary for the splicing of GC-rich, levelled intron/exon architecture. Acute removal of Speckles leads to a drastic downregulation of GC-rich genes which are clustered within GC-rich isochores. Genes outside these domains are physically away from Speckles and are not affected from loss of Speckles. Animal genomes that do not have GC-rich isochores, do not have GC-rich levelled intron/exon architecture and do not have Speckles. Our results suggest that the expansion of Speckles core proteins’ intrinsically disordered domains during vertebrate evolution facilitated GC-content elevation in Amniotes by creating a condensate necessary to splice the by-products of this process: GC-rich, levelled intron/exon architecture.
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Project description:Nuclear Speckles are large, multi-component condensates in the mammalian nuclei that are thought to be involved in various stages of gene expression, including transcription, splicing, and export. Investigating the direct role of Speckles in these processes have been intractable due to their heterogeneous, multi-component nature. Here we show that Speckles are necessary for the splicing of GC-rich, levelled intron/exon architecture. Acute removal of Speckles leads to a drastic downregulation of GC-rich genes which are clustered within GC-rich isochores. Genes outside these domains are physically away from Speckles and are not affected from loss of Speckles. Animal genomes that do not have GC-rich isochores, do not have GC-rich levelled intron/exon architecture and do not have Speckles. Our results suggest that the expansion of Speckles core proteins’ intrinsically disordered domains during vertebrate evolution facilitated GC-content elevation in Amniotes by creating a condensate necessary to splice the by-products of this process: GC-rich, levelled intron/exon architecture.
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Project description:Nuclear Speckles are large, multi-component condensates in the mammalian nuclei that are thought to be involved in various stages of gene expression, including transcription, splicing, and export. Investigating the direct role of Speckles in these processes have been intractable due to their heterogeneous, multi-component nature. Here we show that Speckles are necessary for the splicing of GC-rich, levelled intron/exon architecture. Acute removal of Speckles leads to a drastic downregulation of GC-rich genes which are clustered within GC-rich isochores. Genes outside these domains are physically away from Speckles and are not affected from loss of Speckles. Animal genomes that do not have GC-rich isochores, do not have GC-rich levelled intron/exon architecture and do not have Speckles. Our results suggest that the expansion of Speckles core proteins’ intrinsically disordered domains during vertebrate evolution facilitated GC-content elevation in Amniotes by creating a condensate necessary to splice the by-products of this process: GC-rich, levelled intron/exon architecture.
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