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- W4290804227 abstract "SUMMARY RNA-binding proteins 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 CRIC-seq method to enrich single RBP-mediated in situ RNA-RNA spatial interacting fragments for deep sequencing. We determine hnRNPA1- and PTBP1-mediated RNA-RNA interactions and regulatory mechanisms in HeLa cells. Unexpectedly, 3D RNA map analysis shows that PTBP1-mediated loops in introns preferably promote cassette exon splicing by accelerating asymmetric intron removal, whereas the loops spanning across cassette exon primarily repress splicing. This “positional rule” 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-mediated RNA-RNA interactions in gene regulation and disease." @default.
- W4290804227 created "2022-08-12" @default.
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- W4290804227 date "2022-08-11" @default.
- W4290804227 modified "2023-09-28" @default.
- W4290804227 title "CRIC-seq reveals positional rule of PTBP1-mediated long-range RNA looping in splicing regulation" @default.
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- W4290804227 doi "https://doi.org/10.1101/2022.08.09.503273" @default.
- W4290804227 hasPublicationYear "2022" @default.
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