GSE182808
Oligodendrocyte differentiation alters tRNA modifications and codon-dependent mRNA decay [QuantMseq]
Oligodendrocytes are specialized cells that confer neuronal myelination. Leukodystrophies associated with oligodendrocyte and hypomyelination are known to result when a number of tRNA metabolism genes are mutated. Thus, for unknown reasons, oligodendrocytes may be hypersensitive to perturbations in tRNA biology. In this study, we survey the tRNA transcriptome in the murine oligodendrocytes cell lineage in an effort to understanding the molecular underpinning for human disease. We find that specific tRNAs are hypomodified in oligodendrocytes within or near the anticodon. This hypomodified state may be the result of differential expression of key modification enzymes during oligodendrocyte differentiation. Moreover, we observe a concomitant relationship between tRNA hypomodification and tRNA decoding potential; observing oligodendrocyte specific alterations in codon optimality-mediated mRNA decay and ribosome transit. Our results reveal that oligodendrocytes naturally maintain a delicate, hypersensitized tRNA/mRNA axis. We suggest this axis underlies disease etiology when further insult to tRNA metabolism is introduced. Overall design: tRNA sequencing data (QuantM-seq) of murine Oligodendrocyte Progenitor Cells (OPCs) (3 replicates). Oligodendrocytes (OLs) (2 replicates) and Astrocytes (Astros) (2 replicates)