PXD047019-1

PXD047019 is an original dataset announced via ProteomeXchange.

Title	RNF212B E3 ligase is essential for crossing over maturation and mouse fertility
Description	Meiosis, a reductional cell division, relies on precise initiation, maturation and resolution of crossovers (COs)-connections between homologs chromosomes-to ensure their accurate segregation during metaphase I. This process is finely regulated in eukaryotes by the interplay of RING-E3 ligases such as Rnf212 and Hei10 in mammals. In this study, we functionally characterized a novel RNF212B E3 ligase. RNF212B co-localizes and interacts with RNF212 forming numerous small foci at zygotene. These consolidate into larger foci at mature COs, colocalizing with Hei10 and MLH1 at pachytene on a synapsis-dependent and DSB-independent manner. Moreover, Rnf212b interacts with pro-COs proteins such as Tex11, MSH4 and RPA and other recombination proteins. Genetically, RNF212B foci depend on the presence of RNF212 and MSH4 but not on Hei10 and CNTD1. Rnf212b-deficient and -enzymatic-dead mutant mice exhibit modest synapsis defects a reduction in pro-CO factors (MSH4, TEX11, RPA, MZIP2) and a complete loss of MLH1-staining of COs, resulting in metaphase I with most univalents. Double mutants for RNF212b and RNF212 exhibit an identical phenotype, while double heterozygous demonstrate a dosage-dependent reduction in the number of COs relative to the single mutant, indicating a functional interplay between both paralogs. SUMOylome analysis of testis from Rnf212b mutants and pull-down analysis of Sumo- and Ubiquitin-tagged Hela cells, suggest that RNf212B is a novel E3 ligase with Ubiquitin activity, serving as a crucial factor for CO designation and maturation. This pathway holds physiological significance, with RNF212B and RNF212 genetic variants substantially contributing to the natural variation in genome-wide recombination rates in humans and mammals.
HostingRepository	PRIDE
AnnounceDate	2024-05-31
AnnouncementXML	Submission_2024-05-31_06:49:42.935.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ivo Hendriks
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	sumoylated lysine
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-16 05:56:57	ID requested
⏵ 1	2024-05-31 06:49:43	announced
2	2024-10-22 06:43:27	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: crossing-over, ubiquitylation,Meiotic recombination, chiasma, fertility, SUMOylation, RNF212B, RING E3 ligases, spermatogenesis

Michael Lund Nielsen
contact affiliation	Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact email	michael.lund.nielsen@cpr.ku.dk
lab head
Ivo Hendriks
contact affiliation	Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact email	ivo.a.hendriks@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047019
     1. Label: PRIDE project
     2. Name: RNF212B E3 ligase is essential for crossing over maturation and mouse fertility