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Genome organization around nuclear speckles drives mRNA splicing efficiency

ABSTRACT: Genome organization around nuclear speckles drives mRNA splicing efficiency

PROVIDER: PRJNA1040796 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26840884_1.fastq.gz	Fastqsanger.gz
	SRR26840884_2.fastq.gz	Fastqsanger.gz
	SRR28488201_1.fastq.gz	Fastqsanger.gz
	SRR28488201_2.fastq.gz	Fastqsanger.gz
	SRR28488202_1.fastq.gz	Fastqsanger.gz

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Genome organization around nuclear speckles drives mRNA splicing efficiency

Project description:The nucleus is highly organized such that factors involved in transcription and processing of distinct classes of RNA are organized within specific nuclear bodies. One example is the nuclear speckle, which is defined by high concentrations of protein and non-coding RNA regulators of pre-mRNA splicing. What functional role, if any, speckles might play in the process of mRNA splicing remains unknown. Here we show that genes localized near nuclear speckles display higher spliceosome concentrations, increased spliceosome binding to their pre-mRNAs, and higher co-transcriptional splicing levels relative to genes that are located farther from nuclear speckles. We show that directed recruitment of a pre-mRNA to nuclear speckles is sufficient to increase mRNA splicing levels. Finally, we show that gene organization around nuclear speckles is highly dynamic with differential localization between cell types corresponding to differences in splicing efficiency. Together, our results integrate the longstanding observations of nuclear speckles with the biochemistry of mRNA splicing and demonstrate a critical role for dynamic 3D spatial organization of genomic DNA in driving spliceosome concentrations and controlling the efficiency of mRNA splicing.

2024-03-22 | GSE247833 | GEO

Dynamics of RNA localization to nuclear speckles are connected to splicing efficiency [RNA-Seq]

Project description:Nuclear speckles, a type of membraneless nuclear organelle in higher eukaryotic cells, play a vital role in gene expression regulation. Using the reverse transcription-based RBP binding sites sequencing (ARTR-seq) method, we study human transcripts associated with nuclear speckles. We identify three gene groups whose transcripts demonstrate different speckle localization properties and dynamics – stably enriched in nuclear speckle post-transcriptionally, transiently enriched in speckles at the pre-mRNA stage co-transcriptionally, and not enriched in speckles. We show that nuclear speckles specifically facilitate splicing of speckle-enriched transcripts. We further reveal RNA sequence features contributing to transcript speckle localization, underscoring a tight interplay between genome organization, RNA cis-elements, and transcript speckle enrichment, and connecting transcript speckle localization with splicing logic. Finally, we show that speckles can act as hubs for the regulated retention of introns during cellular stress. Collectively, our data highlight a role of nuclear speckles in both co- and post-transcriptional splicing regulation.

2024-09-05 | GSE255207 | GEO

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Dynamics of RNA localization to nuclear speckles are connected to splicing efficiency [RNA-Seq]

Project description:Dynamics of RNA localization to nuclear speckles are connected to splicing efficiency [RNA-Seq]

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Dynamics of RNA localization to nuclear speckles are connected to splicing efficiency [ARTR-seq]

Project description:Dynamics of RNA localization to nuclear speckles are connected to splicing efficiency [ARTR-seq]

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Nuclear speckles as a key regulator for the 3D genome organization [HiC]

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Nuclear speckles as a key regulator for the 3D genome organization [RNA-Seq]

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RIP-seq analysis for RNAs associated with hTERT in nuclear speckles.

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