Expanded tRNA methyltransferase family member TRMT9B regulates synaptic growth and function
Abstract: Nervous system function rests on the formation of functional synapses between neurons. We have identified TRMT9B as a new regulator of synapse formation and function in Drosophila. TRMT9B has been studied for its role as a tumor suppressor and is one of two metazoan homologs of yeast tRNA methyltransferase 9 (Trm9), which methylates tRNA wobble uridines. Whereas Trm9 homolog ALKBH8 is ubiquitously expressed, TRMT9B is enriched in the nervous system. However, in the absence of animal models, TRMT9B's role in the nervous system has remained unstudied. Here, we generate null alleles of TRMT9B and find it acts postsynaptically to regulate synaptogenesis and promote neurotransmission. Through liquid chromatography‐mass spectrometry, we find that ALKBH8 catalyzes canonical tRNA wobble uridine methylation, raising the question of whether TRMT9B is a methyltransferase. Structural modeling studies suggest TRMT9B retains methyltransferase function and, in vivo, disruption of key methyltransferase residues blocks TRMT9B's ability to rescue synaptic overgrowth, but not neurotransmitter release. These findings reveal distinct roles for TRMT9B in the nervous system and highlight the significance of tRNA methyltransferase family diversification in metazoans.
- Standort
-
Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
-
Online-Ressource
- Sprache
-
Englisch
- Erschienen in
-
Expanded tRNA methyltransferase family member TRMT9B regulates synaptic growth and function ; day:29 ; month:08 ; year:2023 ; extent:17
EMBO reports / European Molecular Biology Organization ; (29.08.2023) (gesamt 17)
- Urheber
-
Hogan, Caley A.
Gratz, Scott J.
Dumouchel, Jennifer L.
Thakur, Rajan S.
Delgado, Ambar
Lentini, Jenna M.
Madhwani, Kimberly R.
Fu, Dragony
O'Connor‐Giles, Kate M.
- DOI
-
10.15252/embr.202356808
- URN
-
urn:nbn:de:101:1-2023083015054638539216
- Rechteinformation
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
14.08.2025, 10:44 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Hogan, Caley A.
- Gratz, Scott J.
- Dumouchel, Jennifer L.
- Thakur, Rajan S.
- Delgado, Ambar
- Lentini, Jenna M.
- Madhwani, Kimberly R.
- Fu, Dragony
- O'Connor‐Giles, Kate M.
Ähnliche Objekte (12)
Mechanism and Function of the Mitochondrial tRNA m3C-Methyltransferase METTL8
The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis
A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription
Multi-layered characterization of the tRNA methyltransferase TRMT2A and its therapeutic potential for polyQ diseases
A human tRNA methyltransferase 9‐like protein prevents tumour growth by regulating LIN9 and HIF1‐α
APP family member dimeric complexes are formed predominantly in synaptic compartments
Crystal structure of tRNA m1A58 methyltransferase TrmI from Aquifex aeolicus in complex with S-adenosyl-l-methionine
Neuronal Histone Methyltransferase EZH2 Regulates Neuronal Morphogenesis, Synaptic Plasticity, and Cognitive Behavior in Mice
A tRNA world
Downregulation of tRNA methyltransferase FTSJ1 by PM2.5 promotes glycolysis and malignancy of NSCLC via facilitating PGK1 expression and translation
Structural basis of tRNA recognition by the m3C RNA methyltransferase METTL6 in complex with SerRS seryl-tRNA synthetase
The RNA methyltransferase METTL8 installs m3C32 in mitochondrial tRNAsThr/Ser(UCN) to optimise tRNA structure and mitochondrial translation
Mechanism and Function of the Mitochondrial tRNA m3C-Methyltransferase METTL8
The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis
A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription
Multi-layered characterization of the tRNA methyltransferase TRMT2A and its therapeutic potential for polyQ diseases
A human tRNA methyltransferase 9‐like protein prevents tumour growth by regulating LIN9 and HIF1‐α
APP family member dimeric complexes are formed predominantly in synaptic compartments
Crystal structure of tRNA m1A58 methyltransferase TrmI from Aquifex aeolicus in complex with S-adenosyl-l-methionine
Neuronal Histone Methyltransferase EZH2 Regulates Neuronal Morphogenesis, Synaptic Plasticity, and Cognitive Behavior in Mice
A tRNA world
Downregulation of tRNA methyltransferase FTSJ1 by PM2.5 promotes glycolysis and malignancy of NSCLC via facilitating PGK1 expression and translation
Structural basis of tRNA recognition by the m3C RNA methyltransferase METTL6 in complex with SerRS seryl-tRNA synthetase
The RNA methyltransferase METTL8 installs m3C32 in mitochondrial tRNAsThr/Ser(UCN) to optimise tRNA structure and mitochondrial translation
Mechanism and Function of the Mitochondrial tRNA m3C-Methyltransferase METTL8
The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis
A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription
Multi-layered characterization of the tRNA methyltransferase TRMT2A and its therapeutic potential for polyQ diseases
A human tRNA methyltransferase 9‐like protein prevents tumour growth by regulating LIN9 and HIF1‐α
APP family member dimeric complexes are formed predominantly in synaptic compartments
Crystal structure of tRNA m1A58 methyltransferase TrmI from Aquifex aeolicus in complex with S-adenosyl-l-methionine
Neuronal Histone Methyltransferase EZH2 Regulates Neuronal Morphogenesis, Synaptic Plasticity, and Cognitive Behavior in Mice
A tRNA world
Downregulation of tRNA methyltransferase FTSJ1 by PM2.5 promotes glycolysis and malignancy of NSCLC via facilitating PGK1 expression and translation
Structural basis of tRNA recognition by the m3C RNA methyltransferase METTL6 in complex with SerRS seryl-tRNA synthetase