PXD025711

PXD025711 is an original dataset announced via ProteomeXchange.

Title	p38-MAPK mediated rRNA processing and translation regulation enables PrE differentiation during mouse blastocyst maturation
Description	p38-MAPKs are stress activated kinases necessary for placental development and nutrient and oxygen transfer during murine post-implantation development. In preimplantation development, p38-MAPK activity is required for blastocyst formation. Additionally, we have previously reported its role in regulating specification of inner cell mass (ICM) towards primitive endoderm (PrE), although a comprehensive mechanistic understanding is currently limited. Adopting live embryo imaging, proteomic and transcriptomic approaches, we report experimental data that directly address this deficit. Chemical inhibition of p38-MAPK activity during blastocyst maturation causes impaired blastocyst cavity expansion, most evident between the third and tenth hours post inhibition onset. We identify an overlapping minimal early blastocyst maturation window of p38-MAPKi inhibition (p38-MAPKi) sensitivity, that is sufficient to impair PrE cell fate by the late blastocyst (E4.5) stage. Comparative proteomic analyses reveal substantial downregulation of ribosomal proteins, the mRNA transcripts of which are also significantly upregulated. Ontological analysis of the differentially expressed transcriptome during this developmental period reveals “translation” related gene transcripts as being most significantly, yet transiently, affected by p38-MAPKi. Moreover, combined assays consistently report concomitant reductions in de novo translation that are associated with accumulation of unprocessed rRNA precursors. Using a phospho-proteomic approach, ± p38-MAPKi, to potentially identify p38-MAPK effectors, we report that clonal siRNA mediated knockdown of Mybpp1a, an rRNA transcription and processing regulator gene, is associated with significantly diminished PrE contribution. Lastly, we show that defective PrE specification caused by p38-MAPKi (but not MEK/ERK signalling inhibition) can be partially rescued by activating the archetypal mTOR mediated translation regulatory pathway. Activated p38-MAPK controls blastocyst maturation in an early and distinctly transient developmental window by regulating gene functionalities related to translation, that creates a permissive environment for appropriate specification of ICM cell fate.
HostingRepository	PRIDE
AnnounceDate	2021-06-28
AnnouncementXML	Submission_2021-06-27_22:23:26.046.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Potesil
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-29 06:47:04	ID requested
⏵ 1	2021-06-27 22:23:26	announced

Bora P, Gahurova L, Ma, š, ek T, Hauserova A, Pot, ě, š, il D, Jansova D, Susor A, Zdr, á, hal Z, Ajduk A, Posp, í, š, ek M, Bruce AW, p38-MAPK-mediated translation regulation during early blastocyst development is required for primitive endoderm differentiation in mice. Commun Biol, 4(1):788(2021) [pubmed]

submitter keyword: human, p38-MAPK, phosphoproteomics, LC-MSMS

Zbynek Zdrahal
contact affiliation	Proteomics Core Facility and Research Group Proteomics, CEITEC-MU, Masaryk University, Brno, Czech Republic
contact email	zdrahal@sci.muni.cz
lab head
David Potesil
contact affiliation	Proteomics Core Facility and Research Group Proteomics CEITEC-MU Masaryk University Brno, Czech Republic
contact email	david.potesil@ceitec.muni.cz
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/06/PXD025711

PRIDE project URI

• PRIDE
  1. PXD025711
     1. Label: PRIDE project
     2. Name: p38-MAPK mediated rRNA processing and translation regulation enables PrE differentiation during mouse blastocyst maturation