Post-transcriptional splicing can occur in a slow-moving zone around the gene
Year: 2023
Type: preprint
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.
Source: eLife
Authors: Allison Coté, Aoife O’Farrell, Ian Dardani, Margaret Dunagin, Chris Coté, Yihan Wan, Sareh Bayatpour, Heather L. Drexler, Katherine A. Alexander, Fei Chen, Asmamaw T. Wassie, Rohan Patel, Kenneth Pham, Edward S. Boyden, Shelley Berger, Jennifer Phillips-Cremins, L. Stirling Churchman, Arjun Raj
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: A plasticity and reprogramming paradigm for therapy resistance at the single cell level, Decoding the bridges and barriers to cellular reprogramming and lineage identity, G1477836796, Engineering and visualizing genome folding at high spatiotemporal resolution, Understanding and Overcoming Resistance to BRAF/MEK Kinase Inhibitors in Melanoma, G4022861566, G4443406907, G5113977847, G5706333659, G6424642065, G6671297155, Center for Photogenomics, G7415145409, Modulation of wild type and mutant p53 by HMGA1, Epigenetic regulation by tumor suppressor p53, CAREER: Unraveling homeostatic mechanisms in gene expression regulation: Integrating research and scientific communication, G8938248483, SPORE in Skin Cancer, G9000001947, G9000003799, G9000027722, G9000049230, G9000060776, G9000077330, G9000111209, G9000127251, G9000138654, G9000157570, G9000193477, G9000222001, G9000322832, G9000331619, G938309714
OpenAlex ID: W4389987697