PXD035346-1

PXD035346 is an original dataset announced via ProteomeXchange.

Title	Branch point evolution controls species-specific alternative splicing and regulates long term potentiation
Description	Regulation and functionality of species-specific alternative splicing has remained enigmatic for many years. Calcium/calmodulin-dependent protein kinase IIβ (CaMKIIβ) is expressed in several splice variants and plays a key role in learning and memory. Here, we identify and characterize several primate-specific CAMK2B splice isoforms, which show altered kinetic properties and changes in substrate specificity. Furthermore, we demonstrate that primate-specific Camk2β alternative splicing is achieved through branch point weakening during evolution. We show that reducing branch point and splice site strength during evolution globally renders constitutive exons alternative, thus providing a paradigm for cis-directed species-specific alternative splicing regulation. Using CRISPR/Cas9 we introduced the weaker human branch point into the mouse genome, resulting in human-like CAMK2B splicing in the brain of mutant mice. We observe a strong impairment of long-term potentiation in CA3-CA1 synapses of mutant mice, thus connecting branch point-controlled, species-specific alternative splicing with a fundamental function in learning and memory.
HostingRepository	PRIDE
AnnounceDate	2022-12-19
AnnouncementXML	Submission_2022-12-19_01:13:05.970.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	YanlongJi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-14 07:24:47	ID requested
⏵ 1	2022-12-19 01:13:06	announced
2	2023-11-14 08:57:08	announced	2023-11-14: Updated project metadata.

submitter keyword: mouse, thiophosphorylation

HenningUrlaub
contact affiliation	Bioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany.
contact email	henning.urlaub@mpinat.mpg.de
lab head
YanlongJi
contact affiliation	Max-Planck-Institute for Biophysical Chemistry
contact email	yanlong.ji@mpibpc.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035346
     1. Label: PRIDE project
     2. Name: Branch point evolution controls species-specific alternative splicing and regulates long term potentiation