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Series GSE203496 Query DataSets for GSE203496
Status Public on May 10, 2023
Title Sites of transcription initiation drive mRNA isoform selection [HumanOrganoids]
Organism Homo sapiens
Experiment type Other
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.
 
Overall design Oxford Nanopore cDNA-PCR sequencing human cerebral organoids, in 3 replicates.
 
Contributor(s) Alfonso-Gonzalez C, Legnini I, Holec S, Arrigoni L, Bönisch U, Rybak-Wolf A, Rajewsky N, Hilgers V
Citation(s) 37178687
Submission date May 20, 2022
Last update date Aug 09, 2023
Contact name Valérie Hilgers
Organization name MPI of Immunobiology and Epigenetics
Street address Stübeweg 51
City Freiburg
ZIP/Postal code 79108
Country Germany
 
Platforms (1)
GPL28975 GridION (Homo sapiens)
Samples (6)
GSM6173951 xmoo1_line_ctrl_1
GSM6173952 xmoo1_line_ctrl_2
GSM6173953 xmoo1_line_ctrl_3
This SubSeries is part of SuperSeries:
GSE203583 Sites of transcription initiation drive mRNA isoform selection
Relations
BioProject PRJNA841011

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE203496_xmoo1_line_pooled.end.corrected.assembly.new.gtf.gz 5.5 Mb (ftp)(http) GTF
GSE203496_xmoo1_line_pooled_assembly.gff.gz 8.5 Mb (ftp)(http) GFF
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Raw data are available in SRA
Processed data are available on Series record

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