PXD025711 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-04-29 06:47:04 | ID requested | |
⏵ 1 | 2021-06-27 22:23:26 | announced | |
Publication List
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] |
Keyword List
submitter keyword: human, p38-MAPK, phosphoproteomics, LC-MSMS |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD025711
- Label: PRIDE project
- Name: p38-MAPK mediated rRNA processing and translation regulation enables PrE differentiation during mouse blastocyst maturation