PXD026407-1

PXD026407 is an original dataset announced via ProteomeXchange.

Title	Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin
Description	Neurons critically rely on the functions of RNA-binding proteins to maintain their polarity and resistance to neurotoxic stresses. HnRNP R has a diverse range of post-transcriptional regulatory functions and is important for neuronal development by regulating axon growth. Hnrnpr pre-mRNA undergoes alternative splicing to produce transcripts encoding two isoforms: a full-length protein and a shorter form lacking the N-terminal acidic domain. While the neuronal defects produced by total hnRNP R depletion have been investigated before, the individual functions of each hnRNP R isoforms are unknown. We generated a Hnrnpr knockout mouse (Hnrnprtm1a/tm1a) showing selective loss of the full-length hnRNP R isoform. Motoneurons cultured from Hnrnprtm1a/tm1a mice did not show any axonal growth defects. However, they show an accumulation of double-strand breaks and an impaired DNA damage response. Proteomic analysis of the hnRNP R interactome revealed the multifunctional protein Yb1 as a top interactor. Yb1 depleted motoneurons also exhibit defects in DNA damage repair. We show that Yb1 is recruited to chromatin upon DNA damage, a mechanism that is dependent on full-length hnRNP R. Our findings thus suggest a novel role of hnRNP R in maintaining genomic integrity and highlight the function of its Nterminal acidic domain in this context.
HostingRepository	PRIDE
AnnounceDate	2021-11-01
AnnouncementXML	Submission_2021-11-01_07:49:54.472.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-01 21:58:11	ID requested
⏵ 1	2021-11-01 07:49:54	announced

Dataset with its publication pending

submitter keyword: hnRNP R, Yb1, DNA damage, motoneuron

Matthias Mann
contact affiliation	Max-Planck-Institute of Biochemistry
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026407
     1. Label: PRIDE project
     2. Name: Loss of full-length hnRNP R isoform impairs DNA damage response in motoneurons by inhibiting Yb1 recruitment to chromatin