PXD058827-1

PXD058827 is an original dataset announced via ProteomeXchange.

Title	Selective RNA sequestration in P-bodies regulates cell identity
Description	Post-transcriptional regulation is pivotal in guiding the gene expression programs that instruct cell fate decisions. Recent studies emphasize the significance of biomolecular condensates in modulating gene expression through RNA processing and translational control. However, the functional roles of RNA condensates in the context of cell fate specification are unknown. In this study, we profiled the coding and non-coding transcriptome within intact biomolecular condensates known as P-bodies in diverse developmental contexts and vertebrate species. Our analyses revealed the conserved, cell type-specific sequestration of RNAs encoding key cell fate specifiers. Notably, P-body contents did not directly reflect gene expression profiles for a given cell type, but rather were enriched for transcripts characteristic of the preceding developmental stage, which are translationally suppressed and stored within P-bodies. We demonstrate that the forced degradation of P-bodies stimulates the translation of transcripts encoding fate-instructive factors, ultimately re-activating a totipotency transcriptional program in human and mouse pluripotent cells. Mechanistically, microRNAs (miRNAs) facilitate the sequestration of specific RNAs into P-bodies in a context-dependent manner. Accordingly, perturbing AGO2, alternative polyadenylation, and miRNA function profoundly reshapes the RNA content of P-bodies and alters cell fate. Furthermore, we show that adding a miRNA target sequence is sufficient to redirect transcripts to P-bodies and influence stem cell self-renewal. Collectively, our findings establish a direct link between biomolecular condensates and cell fate decisions across vertebrate species.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_06:11:15.362.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alicia Richards
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-12 14:24:41	ID requested
⏵ 1	2025-05-07 06:11:16	announced

10.1126/sciadv.adt7836;

Detomasi TC, Degotte G, Huang S, Suryawanshi RK, Diallo A, Lizzadro L, Zaptero-Belinch, ó, n FJ, Taha TY, Li J, Richards AL, Hantz ER, Alam Z, Montano M, McCavitt-Malvido M, Gumpena R, Partridge JR, Correy GJ, Matsui Y, Charvat AF, Glenn IS, Rosecrans J, Revalde JL, Anderson D, Hultquist JF, Arkin MR, Neitz RJ, Swaney DL, Krogan NJ, Shoichet BK, Verba KA, Ott M, Renslo AR, Craik CS, inhibitors with potent in vivo efficacy. Sci Adv, 11(17):eadt7836(2025) [pubmed]

submitter keyword: P-bodies, proteomics, stem cells

DanielleL Swaney
contact affiliation	Cellular and Molecular Pathology, UCSF
contact email	Danielle.swaney@ucsf.edu
lab head
Alicia Richards
contact affiliation	Krogan lab
contact email	alicia.richards@ucsf.edu
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/2025/05/PXD058827

PRIDE project URI

• PRIDE
  1. PXD058827
     1. Label: PRIDE project
     2. Name: Selective RNA sequestration in P-bodies regulates cell identity