PXD051516-2

PXD051516 is an original dataset announced via ProteomeXchange.

Title	Functional antagonism between Mir483 and its host gene Igf2 in the control of developmental growth
Description	Many mammalian microRNAs are embedded within introns of protein-coding genes, yet their functional relationship with the host gene is poorly understood. Here we identify Mir483, as having opposing developmental and physiological roles to those of its host gene, the paternally-expressed Igf2. Mechanistically, Mir483 expression is dependent on Igf2 transcription and the epigenetic regulation of the Igf2/H19 imprinting control region. Mir483 deletion in vivo resulted in normal growth, but induced distinct molecular signatures. Transgenic Mir483 overexpression in utero caused fetal, but not placental, growth restriction and cardiovascular defects leading to fetal demise. Overexpression of Mir483 postnatally resulted in growth stunting through IGF1 repression, increased hepatic lipid production, and excessive adiposity. IGF1 infusion rescued the post-natal growth restriction. Our data highlight a novel functional antagonism between a growth-suppressor microRNA and its growth-promoting host gene. We suggest that Mir483 was evolutionary co-opted to provide exquisite control of IGF signalling activity.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:58:11.742.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Robin Antrobus
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-16 20:56:33	ID requested
1	2024-09-12 10:13:49	announced
⏵ 2	2024-10-22 06:58:12	announced	2024-10-22: Updated project metadata.

10.1016/J.CELREP.2024.114750;

submitter keyword: growth,Mouse, TMT, microRNA, quantitative proteomics

Miguel Constância
contact affiliation	1Medical Research Council Metabolic Diseases Unit, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom
contact email	jmasmc2@cam.ac.uk
lab head
Robin Antrobus
contact affiliation	CIMR medicine
contact email	pra29@cam.ac.uk
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/2024/09/PXD051516

PRIDE project URI

• PRIDE
  1. PXD051516
     1. Label: PRIDE project
     2. Name: Functional antagonism between Mir483 and its host gene Igf2 in the control of developmental growth