Longan Emery R, Ramos Jillian, Fu Dragony
University of Rochester, Department of Biology, Rochester, NY 14620.
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, CO 80045.
MicroPubl Biol. 2023 Jan 16;2023. doi: 10.17912/micropub.biology.000675. eCollection 2023.
The conversion of adenosine to inosine at the wobble position of select tRNAs is essential for decoding specific codons in bacteria and eukarya. In eukarya, wobble inosine modification is catalyzed by the heterodimeric ADAT complex containing ADAT2 and ADAT3. Human individuals homozygous for loss of function variants in ADAT3 exhibit intellectual disability disorders. We created a flexible computational tool to scan the human, mouse, nematode, fruit fly, and yeast exomes for genes either enriched or depleted in ADAT-dependent codons as compared to background models of codon bias derived from the exomes themselves. We find that many genes are enriched or depleted for ADAT-dependent codons as compared to the genomic background in all five species. Among those genes enriched for ADAT-dependent codons in humans, we find there is significant Gene Ontology (GO) enrichment for genes involved in diverse neurological processes. This pattern persists in the mouse exome but not the fruit fly or nematode exome. In the nematode exome, genes enriched in ADAT-dependent codons are GO enriched for translation associated genes, and in yeast there is GO enrichment for genes involved in metabolic functions. There is also GO-term overlap between yeast and fruit flies. Importantly, in its generalized form, ADATscan can also be used to scan any exome for genes enriched in any subset of codons specified by the user.
在特定tRNA的摆动位置将腺苷转化为肌苷对于细菌和真核生物中特定密码子的解码至关重要。在真核生物中，摆动肌苷修饰由包含ADAT2和ADAT3的异二聚体ADAT复合物催化。ADAT3功能丧失变体纯合的人类个体表现出智力残疾障碍。我们创建了一个灵活的计算工具，用于扫描人类、小鼠、线虫、果蝇和酵母的外显子组，以寻找与源自外显子组本身的密码子偏好背景模型相比，在依赖ADAT的密码子中富集或耗尽的基因。我们发现，与所有五个物种的基因组背景相比，许多基因在依赖ADAT的密码子中富集或耗尽。在人类中那些在依赖ADAT的密码子中富集的基因中，我们发现参与各种神经过程的基因有显著的基因本体论（GO）富集。这种模式在小鼠外显子组中持续存在，但在果蝇或线虫外显子组中不存在。在线虫外显子组中，在依赖ADAT的密码子中富集的基因在与翻译相关的基因上有GO富集，而在酵母中，参与代谢功能的基因有GO富集。酵母和果蝇之间也有GO术语重叠。重要的是，以其通用形式，ADATscan还可用于扫描任何外显子组，以寻找在用户指定的任何密码子子集中富集的基因。
