Cell-type-specific expression of tRNAs in the brain regulates cellular homeostasis

被引：0

作者：

Kapur, Mridu ^{[1
,2
]}

Molumby, Michael J. ^{[1
,2
]}

Guzman, Carlos ^{[3
,4
]}

Heinz, Sven ^{[3
,4
]}

Ackerman, Susan L. ^{[1
,2
,5
]}

机构：

[1] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

[2] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[3] Univ Calif San Diego, Sch Med, Dept Med, Div Endocrinol, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Dept Bioengn, Bioinformat & Syst Biol Grad Program, La Jolla, CA 92093 USA

[5] Univ Calif San Diego, Dept Neurobiol, Div Biol Sci, La Jolla, CA 92093 USA

来源：

NEURON | 2024年 / 112卷 / 09期

基金：

美国国家卫生研究院;

关键词：

MESSENGER-RNA; TRANSCRIPTION FACTORS; CRE RECOMBINASE; POL II; TRANSLATION; GENES; NEURONS; BINDING; EFFICIENT; CHROMATIN;

D O I：

10.1016/j.neuron.2024.01.028

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Defects in tRNA biogenesis are associated with multiple neurological disorders, yet our understanding of these diseases has been hampered by an inability to determine tRNA expression in individual cell types within a complex tissue. Here, we developed a mouse model in which RNA polymerase III is conditionally epitope tagged in a Cre-dependent manner, allowing us to accurately profile tRNA expression in any cell type in vivo . We investigated tRNA expression in diverse nervous system cell types, revealing dramatic heterogeneity in the expression of tRNA genes between populations. We found that while maintenance of levels of tRNA isoacceptor families is critical for cellular homeostasis, neurons are differentially vulnerable to insults to distinct tRNA isoacceptor families. Cell -type -specific translatome analysis suggests that the balance between tRNA availability and codon demand may underlie such differential resilience. Our work provides a platform for investigating the complexities of mRNA translation and tRNA biology in the brain.

引用

页码：1397 / 1415.e6

页数：26

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