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Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE210583 | GEO | 2023/03/22

REPOSITORIES: GEO

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Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation [RIC-seq]

Project description:RNA-binding proteins (RBPs) bind at different positions of pre-mRNA molecules to promote or reduce the usage of a particular exon. Seeking to understand the working principle of these positional effects, we develop a capture RIC-seq (CRIC-seq) method to enrich specific RBP-associated in situ proximal RNA-RNA fragments for deep sequencing. We determine hnRNPA1-, SRSF1-, and PTBP1-associated proximal RNA-RNA contacts and regulatory mechanisms in HeLa cells. Unexpectedly, the 3D RNA map analysis shows that PTBP1-associated loops in individual introns preferentially promote cassette exon splicing by accelerating asymmetric intron removal, whereas the loops spanning across cassette exon primarily repress splicing. These “positional rules” can faithfully predict PTBP1-regulated splicing outcomes. We further demonstrate that cancer-related splicing quantitative trait loci can disrupt RNA loops by reducing PTBP1 binding on pre-mRNAs to cause aberrant splicing in tumors. Our study presents a powerful method for exploring the functions of RBP-associated RNA-RNA proximal contacts in gene regulation and disease.

2023-03-22 | GSE222816 | GEO

Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation [SELEX]

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Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation [RNA-seq]

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Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation [CRIC-seq]

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Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation

Project description:Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation

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Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation [RIC-seq]

Project description:Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation [RIC-seq]

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Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation [SELEX]

Project description:Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation [SELEX]

| PRJNA866368 | ENA

Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation [RNA-seq]

Project description:Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation [RNA-seq]

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Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation [CRIC-seq]

Project description:Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation [CRIC-seq]

| PRJNA866367 | ENA

Intronic splicing enhancers, cognate splicing factors and context-dependent regulation rules.

Project description:Most human genes produce multiple splicing isoforms with distinct functions. To systematically understand splicing regulation, we conducted an unbiased screen and identified >100 intronic splicing enhancers (ISEs), clustered by sequence similarity. All ISEs functioned in multiple cell types and in heterologous introns, and patterns of distribution and conservation across pre-mRNA regions were similar to those of exonic splicing silencers. Consistently, all ISEs inhibited use of splice sites from exons. Putative trans-factors of each ISE group were identified and validated. Five distinct groups were recognized by hnRNP H and hnRNP F, whose C-terminal domains were sufficient to render context-dependent activities of ISEs. The sixth group was controlled by factors that either activate or suppress splicing. We provide a comprehensive picture of general ISE activities and suggest new models of how single elements can function oppositely, depending on locations and binding factors.

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