神经系统功能依赖于神经元之间功能突触的形成。我们已经确认TRMT9B是果蝇突触形成和功能的新调节因子。TRMT9B已经被研究其作为肿瘤抑制因子的作用，它是酵母tRNA甲基转移酶9 (Trm9)的两个后生动物同源物之一，它能甲基化tRNA的游动尿嘧啶。虽然Trm9同源物ALKBH8广泛表达，但TRMT9B在神经系统中富集。然而，在缺乏动物模型的情况下，TRMT9B在神经系统中的作用尚未研究。在这里，我们产生了TRMT9B的缺失等位基因，并发现它在突触后调节突触发生并促进神经递质传递。通过液相色谱-质谱法，我们发现ALKBH8能催化经典的tRNA游动尿嘧啶甲基化，这引发了TRMT9B是否为甲基转移酶的疑问。结构建模研究表明TRMT9B保留甲基转移酶功能，在体内，关键甲基转移酶残基的破坏阻断了TRMT9B救治突触过度增生的能力，但不影响神经递质释放。这些发现揭示了TRMT9B在神经系统中的不同作用，并突显了甲基转移酶家族在后生动物中的重要意义。© 2023 The Authors. 根据CC BY NC ND 4.0协议发布。

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.© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.