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Expanded tRNA methyltransferase family member TRMT9B regulates synaptic growth and function

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 methyltran...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10561368/
https://www.ncbi.nlm.nih.gov/pubmed/37642556
http://dx.doi.org/10.15252/embr.202356808
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author 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
author_facet 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
author_sort Hogan, Caley A
collection PubMed
description 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.
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spelling pubmed-105613682023-10-10 Expanded tRNA methyltransferase family member TRMT9B regulates synaptic growth and function 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 EMBO Rep Articles 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. John Wiley and Sons Inc. 2023-08-29 /pmc/articles/PMC10561368/ /pubmed/37642556 http://dx.doi.org/10.15252/embr.202356808 Text en © 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Articles
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
Expanded tRNA methyltransferase family member TRMT9B regulates synaptic growth and function
title Expanded tRNA methyltransferase family member TRMT9B regulates synaptic growth and function
title_full Expanded tRNA methyltransferase family member TRMT9B regulates synaptic growth and function
title_fullStr Expanded tRNA methyltransferase family member TRMT9B regulates synaptic growth and function
title_full_unstemmed Expanded tRNA methyltransferase family member TRMT9B regulates synaptic growth and function
title_short Expanded tRNA methyltransferase family member TRMT9B regulates synaptic growth and function
title_sort expanded trna methyltransferase family member trmt9b regulates synaptic growth and function
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10561368/
https://www.ncbi.nlm.nih.gov/pubmed/37642556
http://dx.doi.org/10.15252/embr.202356808
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