Post-transcriptional splicing can occur in a slow-moving zone around the gene

Coté, Allison, O'Farrell, Aoife, Dardani, Ian, Dunagin, Margaret, Coté, Chris, Wan, Yihan, Bayatpour, Sareh, Drexler, Heather L, Alexander, Katherine A, Chen, Fei, Wassie, Asmamaw T, Patel, Rohan, Pham, Kenneth, Boyden, Edward S, Berger, Shelly, Phillips-Cremins, Jennifer, Churchman, L Stirling, Raj, Arjun (April 2024) Post-transcriptional splicing can occur in a slow-moving zone around the gene. eLife, 12. ISSN 2050-084X (Public Dataset)

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Abstract

Splicing is the stepwise molecular process by which introns are removed from pre-mRNA and exons are joined together to form mature mRNA sequences. The ordering and spatial distribution of these steps remain controversial, with opposing models suggesting splicing occurs either during or after transcription. We used single-molecule RNA FISH, expansion microscopy, and live-cell imaging to reveal the spatiotemporal distribution of nascent transcripts in mammalian cells. At super-resolution levels, we found that pre-mRNA formed clouds around the transcription site. These clouds indicate the existence of a transcription-site-proximal zone through which RNA move more slowly than in the nucleoplasm. Full-length pre-mRNA undergo continuous splicing as they move through this zone following transcription, suggesting a model in which splicing can occur post-transcriptionally but still within the proximity of the transcription site, thus seeming co-transcriptional by most assays. These results may unify conflicting reports of co-transcriptional versus post-transcriptional splicing.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA expression bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > introns bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mRNA bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA splicing
CSHL Authors:	Alexander, Katherine
Communities:	CSHL labs > Alexander lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	5 April 2024
Date Deposited:	16 Jul 2024 14:57
Last Modified:	16 Jul 2024 14:57
PMCID:	PMC10997330
Related URLs:	Publisher
Dataset ID:	https://doi.org/10.5061/dryad.m0cfxppb7 GEO: GSE254859
URI:	https://repository.cshl.edu/id/eprint/41611

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