METTL9 sustains vertebrate neural development primarily via non-catalytic functions

Azzurra Codino, Luca Spagnoletti, Claudia Olobardi, Alessandro Cuomo, Helena Santos-Rosa, Martina Palomba, Natasha Margaroli, Stefania Girotto, Rita Scarpelli, Shi-Lu Luan, Eleonora Crocco, Paolo Bianchini, Andrew J. Bannister, Stefano Gustincich, Tony Kouzarides, Riccardo Rizzo, Isaia Barbieri, Federico Cremisi, Robert Vignali and Luca Pandolfini ()
Additional contact information
Azzurra Codino: Via Enrico Melen 83
Luca Spagnoletti: Via Enrico Melen 83
Claudia Olobardi: via Luca Ghini 13
Alessandro Cuomo: European Institute of Oncology IRCCS
Helena Santos-Rosa: Tennis Court Road
Martina Palomba: Via Morego 30
Natasha Margaroli: Via Morego 30
Stefania Girotto: Via Morego 30
Rita Scarpelli: Via Morego 30
Shi-Lu Luan: 10 Tennis Court Road
Eleonora Crocco: Via Giuseppe Moruzzi
Paolo Bianchini: Via Enrico Melen 83
Andrew J. Bannister: Tennis Court Road
Stefano Gustincich: Via Enrico Melen 83
Tony Kouzarides: Tennis Court Road
Riccardo Rizzo: Via Monteroni
Isaia Barbieri: 10 Tennis Court Road
Federico Cremisi: Via Giuseppe Moruzzi
Robert Vignali: via Luca Ghini 13
Luca Pandolfini: Via Enrico Melen 83

Nature Communications, 2025, vol. 16, issue 1, 1-29

Abstract: Abstract METTL9 is an enzyme catalysing N1-methylation of histidine residues (1MH) within eukaryotic proteins. Given its high expression in vertebrate nervous system and its potential association with neurodevelopmental delay, we dissected Mettl9 role during neural development. We generated three distinct mouse embryonic stem cell lines: a complete Mettl9 knock-out (KO), an inducible METTL9 Degron and a line endogenously expressing a catalytically inactive protein, and assessed their ability to undergo neural differentiation. In parallel, we down-regulated mettl9 in Xenopus laevis embryos and characterised their neural development. Our multi-omics data indicate that METTL9 exerts a conserved role in sustaining vertebrate neurogenesis. This is largely independent of its catalytic activity and occurs through modulation of the secretory pathway. METTL9 interacts with key regulators of cellular transport, endocytosis and Golgi integrity; moreover, in Mettl9KO cells Golgi becomes fragmented. Overall, we demonstrate a developmental function of Mettl9 and link it to a 1MH-independent pathway, namely, the maintenance of the secretory system, which is essential throughout neural development.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62414-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62414-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62414-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().