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.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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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)
- Creator
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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
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10.15252/embr.202356808
- URN
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urn:nbn:de:101:1-2023083015054638539216
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:44 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- 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.
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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
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