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| Status |
Public on Apr 25, 2024 |
| Title |
KIS counteracts PTBP2 and regulates alternative exon usage in neurons |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Alternative RNA splicing is an essential and dynamic process in neuronal differentiation and synapse maturation, and dysregulation of this process has been associated with neurodegenerative diseases. Recent studies have revealed the importance of RNA-binding proteins in the regulation of neuronal splicing programs. However, the molecular mechanisms involved in the control of these splicing regulators are still unclear. Here we show that KIS, a kinase upregulated in the developmental brain, imposes a genome-wide alteration in exon usage during neuronal differentiation. KIS contains a protein-recognition domain common to spliceosomal components and phosphorylates PTBP2, counteracting the role of this splicing factor in exon exclusion. At the molecular level, phosphorylation of unstructured domains within PTBP2 causes its dissociation from two co-regulators, Matrin3 and hnRNPM, and hinders the RNA-binding capability of the complex. Furthermore, KIS and PTBP2 display strong and opposing functional interactions in synaptic spine emergence and maturation. Taken together, our data uncover a post-translational control of splicing regulators that link transcriptional and alternative exon usage programs in neuronal development.
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| Overall design |
To analyze the role of KIS in genome-wide exon usage during neuronal differentiation in vitro we infected cortical neurons at 7DIV with lentiviral constructs co-expressing GFP and a shRNA targeted against KIS or a control shRNA, and collected them at 18DIV to obtain total RNA from triplicate samples for deep sequencing analysis.
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| Contributor(s) |
Moreno-Aguilera M, Gallego C |
| Citation(s) |
38597390 |
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| Submission date |
Mar 04, 2024 |
| Last update date |
Apr 25, 2024 |
| Contact name |
Carme Gallego |
| E-mail(s) |
cggbmc@ibmb.csic.es
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| Organization name |
IBMB-CSIC
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| Street address |
Baldiri Reixac 15 3-A16
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| City |
Barcelona |
| State/province |
Catalonia |
| ZIP/Postal code |
08028 |
| Country |
Spain |
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| Platforms (1) |
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| Samples (6)
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| GSM8124634 |
18DIV cortical neurons, ctrl shRNA, replica A1 |
| GSM8124635 |
18DIV cortical neurons, ctrl shRNA, replica A2 |
| GSM8124636 |
18DIV cortical neurons, ctrl shRNA, replica A3 |
| GSM8124637 |
18DIV cortical neurons, KIS shRNA, replica B1 |
| GSM8124638 |
18DIV cortical neurons, KIS shRNA, replica B2 |
| GSM8124639 |
18DIV cortical neurons, KIS shRNA, replica B3 |
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| Relations |
| BioProject |
PRJNA1083502 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE260790_Exon_reads.csv.gz |
3.9 Mb |
(ftp)(http) |
CSV |
| GSE260790_Gene_reads.csv.gz |
3.1 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
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