Co-transcriptional splicing regulates 3' end cleavage during mammalian erythropoiesis
| Autor: | Karen Adelman, Claudia A. Mimoso, Karla M. Neugebauer, Kirsten A. Reimer |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Transcription Elongation
Genetic RNA Splicing RNA polymerase II beta-Globins medicine.disease_cause Cleavage (embryo) Article 03 medical and health sciences Exon Mice 0302 clinical medicine Erythroid Cells Transcription (biology) Cell Line Tumor medicine Leukocytes Animals Humans Erythropoiesis Molecular Biology Gene 030304 developmental biology RNA Cleavage Mutation 0303 health sciences biology Base Sequence Chemistry beta-Thalassemia Intron Cell Differentiation Cell Biology Exons Introns Cell biology RNA splicing biology.protein Spliceosomes RNA Polymerase II RNA Splice Sites 030217 neurology & neurosurgery |
| Zdroj: | Mol Cell |
| ISSN: | 1097-4164 |
| Popis: | Pre-mRNA processing steps are tightly coordinated with transcription in many organisms. To determine how co-transcriptional splicing is integrated with transcription elongation and 3’ end formation in mammalian cells, we performed long-read sequencing of individual nascent RNAs and PRO-seq during mouse erythropoiesis. Splicing was not accompanied by transcriptional pausing and was detected when RNA polymerase II (Pol II) was within 75 – 300 nucleotides of 3’ splice sites (3’SSs), often during transcription of the downstream exon. Interestingly, several hundred introns displayed abundant splicing intermediates, suggesting that splicing delays can take place between the two catalytic steps. Overall, splicing efficiencies were correlated among introns within the same transcript, and intron retention was associated with inefficient 3’ end cleavage. Remarkably, a thalassemia patient-derived mutation introducing a cryptic 3’SS improves both splicing and 3’ end cleavage of individual β-globin transcripts, demonstrating functional coupling between the two co-transcriptional processes as a determinant of productive gene output. |
| Databáze: | OpenAIRE |
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