PXD050320

PXD050320 is an original dataset announced via ProteomeXchange.

Title	KIS counteracts PTBP2 and regulates alternative exon usage in neurons
Description	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.
HostingRepository	PRIDE
AnnounceDate	2024-04-25
AnnouncementXML	Submission_2024-04-25_02:18:27.497.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Carme Gallego
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-04 04:52:41	ID requested
⏵ 1	2024-04-25 02:18:27	announced

10.7554/ELIFE.96048;

submitter keyword: KIS kinase

PTBP2

alternative splicing

exon usage

neuronal differentiation

RNA binding

PSD95

synaptic activity

Carme Gallego
contact affiliation	Molecular Biology Institute of Barcelona (IBMB), CSIC, Catalonia, Spain
contact email	cggbmc@ibmb.csic.es
lab head
Carme Gallego
contact affiliation	Institut de Biologia Molecular de Barcelona, CSIC
contact email	cggbmc@ibmb.csic.es
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050320
     1. Label: PRIDE project
     2. Name: KIS counteracts PTBP2 and regulates alternative exon usage in neurons