|
| Status |
Public on Oct 01, 2020 |
| Title |
Exon-activated functional rescue secures neuronal transcript signatures |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The production of alternative RNA variants contributes to the tissue-specific regulation of gene expression. In the animal nervous system, a shift towards more distal 3’ processing sites generates hundreds of substantially extended messenger RNAs. These neuronal transcript signatures are crucial for nervous system development and function. However, no clear understanding of the mechanism of systematic 3’ extension in neurons has yet been achieved. Here, we report that the highly conserved RNA-binding protein ELAV globally regulates all events of neuronal 3’ end processing by directly binding to the proximal 3’ end of its target RNAs. We uncover an endogenous strategy of functional gene rescue, by which neuronal RNA signatures are safeguarded in a loss-of-function context. When not directly repressed by ELAV, the transcript encoding the ELAV paralogue FNE acquires a mini‑exon, which equips the new FNE protein with the ability to translocate to the nucleus and rescue neuronal 3’ end processing. We propose that exon-activated functional rescue is a widespread mechanism that ensures robustness of processes that are regulated by a hierarchy, rather than by redundancy, of effectors.
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| |
|
| Overall design |
Analysis of alternative polyadenyation using RNA-seq and Clip-seq data
|
| |
|
| Contributor(s) |
Hilgers V, Carrasco J |
| Citation |
https://0-doi-org.brum.beds.ac.uk/10.1016/j.molcel.2020.09.011
|
| Submission date |
Mar 14, 2020 |
| Last update date |
Oct 01, 2020 |
| Contact name |
Valérie Hilgers |
| Organization name |
MPI of Immunobiology and Epigenetics
|
| Street address |
Stübeweg 51
|
| City |
Freiburg |
| ZIP/Postal code |
79108 |
| Country |
Germany |
| |
|
| Platforms (3) |
| GPL21306 |
Illumina HiSeq 4000 (Drosophila melanogaster) |
| GPL23323 |
Illumina HiSeq 3000 (Drosophila melanogaster) |
| GPL25244 |
Illumina NovaSeq 6000 (Drosophila melanogaster) |
|
| Samples (62)
|
|
| Relations |
| BioProject |
PRJNA612625 |
| SRA |
SRP252814 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE146986_RNA-seq.wildtype.tpm.tsv.gz |
477.0 Kb |
(ftp)(http) |
TSV |
| GSE146986_Segments_split.early.gff.gz |
1.3 Mb |
(ftp)(http) |
GFF |
| GSE146986_Segments_split.late.gff.gz |
1.3 Mb |
(ftp)(http) |
GFF |
| GSE146986_elav-_fne-rbp9_wt.early.APA_targets.tsv.gz |
30.0 Kb |
(ftp)(http) |
TSV |
| GSE146986_elav-_fne_wt.early.APA_targets.tsv.gz |
24.9 Kb |
(ftp)(http) |
TSV |
| GSE146986_elav-_fne_wt.late.APA_targets.tsv.gz |
18.5 Kb |
(ftp)(http) |
TSV |
| GSE146986_elav-nfne_wt.early.apa_targets.gene.tsv.gz |
9.9 Kb |
(ftp)(http) |
TSV |
| GSE146986_elav-nfne_wt.late.apa_targets.gene.tsv.gz |
9.9 Kb |
(ftp)(http) |
TSV |
| GSE146986_elav-rbp9_wt.early.APA_targets.tsv.gz |
16.1 Kb |
(ftp)(http) |
TSV |
| GSE146986_elav_iclip.NNNGGTTNN_cDNA_peaks.bedgraph.gz |
1.4 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE146986_elav_iclip.NNNGGTTNN_cDNA_peaks.intronic.bedgraph.gz |
805.6 Kb |
(ftp)(http) |
BEDGRAPH |
| GSE146986_elav_iclip.NNNTGGCNN_cDNA_peaks.bedgraph.gz |
2.4 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE146986_elav_iclip.NNNTGGCNN_cDNA_peaks.intronic.bedgraph.gz |
1.2 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE146986_elav_wt.early.APA_targets.tsv.gz |
19.9 Kb |
(ftp)(http) |
TSV |
| GSE146986_elav_wt.late.APA_targets.tsv.gz |
8.0 Kb |
(ftp)(http) |
TSV |
| GSE146986_fne-rbp9_wt.early.APA_targets.tsv.gz |
4.4 Kb |
(ftp)(http) |
TSV |
| GSE146986_fne_wt.early.APA_targets.tsv.gz |
6.4 Kb |
(ftp)(http) |
TSV |
| GSE146986_fne_wt.late.APA_targets.tsv.gz |
1.1 Kb |
(ftp)(http) |
TSV |
| GSE146986_nfne_wt.early.apa_targets.gene.tsv.gz |
9.7 Kb |
(ftp)(http) |
TSV |
| GSE146986_nfne_wt.late.apa_targets.gene.tsv.gz |
9.6 Kb |
(ftp)(http) |
TSV |
| GSE146986_rbp9_wt.early.APA_targets.tsv.gz |
905 b |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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