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| Status |
Public on May 10, 2023 |
| Title |
Sites of transcription initiation drive mRNA isoform selection [FLAMseq] |
| Organism |
Drosophila melanogaster |
| Experiment type |
Other
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| Summary |
The generation of distinct messenger RNA isoforms through alternative splicing and alternative 3' end formation influences the expression and function of genes, often in a cell-type specific manner. Here, we quantitatively assess the regulatory relationships between transcription initiation and co-transcriptional processing steps, particularly 3' end formation. Applying multiple long-read-sequencing approaches to obtain an assembly accurately representing even the longest mRNA isoforms from end-to-end, we quantify mRNA isoform choice in Drosophila and human tissues, including the transcriptionally complex nervous system. We find that in Drosophila brains as well as in human cerebral organoids, 3' end site choice is globally influenced by the site of transcription start. We define a subset of TSSs, “dominant promoters” that impose a transcriptional constraint to predetermine splice and polyadenylation variants, which are characterized by specific epigenetic signatures. In vivo deletion or overexpression of dominant promoters disrupted the 3' end expression landscape. Our study demonstrates the crucial impact of transcription initiation site choice on the regulation of transcript diversity and tissue identity.
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| Overall design |
FLAM-sequencing of wild type (w1118) Drosophila melanogaster heads, 3 replicates
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| Contributor(s) |
Alfonso-Gonzalez C, Legnini I, Holec S, Arrigoni L, Bönisch U, Rybak-Wolf A, Rajewsky N, Hilgers V |
| Citation(s) |
37178687 |
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| Submission date |
May 19, 2022 |
| Last update date |
Aug 09, 2023 |
| Contact name |
Valérie Hilgers |
| Organization name |
MPI of Immunobiology and Epigenetics
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| Street address |
Stübeweg 51
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| City |
Freiburg |
| ZIP/Postal code |
79108 |
| Country |
Germany |
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| Platforms (1) |
| GPL28354 |
Sequel (Drosophila melanogaster) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE203583 |
Sites of transcription initiation drive mRNA isoform selection |
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| Relations |
| BioProject |
PRJNA839734 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE203390_RAW.tar |
4.4 Mb |
(http)(custom) |
TAR (of CSV) |
| GSE203390_w1118_heads_flam-seq_pooled.isoforms.gtf.gz |
298.7 Kb |
(ftp)(http) |
GTF |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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