Transfer RNA functionality not only impacts the rate by which an mRNA is read by the ribosome, but it also is a major determinant of the mRNA’s stability. This concept is termed c odon optimality which is defined broadly as the non-uniform decoding rate, determined (in part) by the functional concentration of tRNAs 1, 2, 3. Thus, for many reasons, some codons/tRNA combinations are more optimal relative to others. Moreover, codon context can influence decoding in similar ways. Depending on functional tRNA concentrations decoding speed, efficiency and accuracy for each codon varies.
#Hcl density code#
We suggest this axis is a potential mediator of pathology in leukodystrophies and white matter disease when further insult to tRNA metabolism is introduced.ĭeciphering the genetic code involves transfer RNA (tRNA) selection by the ribosome to match a cognate codon displayed in the ribosomal A-site. Our results reveal that oligodendrocytes naturally maintain a delicate, hypersensitized tRNA/mRNA axis. 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. This hypomodified state may be the result of differential expression of key modification enzymes during oligodendrocyte differentiation. In this study, we survey the tRNA transcriptome in the murine oligodendrocyte cell lineage and find that specific tRNAs are hypomodified in oligodendrocytes within or near the anticodon compared to oligodendrocyte progenitor cells (OPCs). Thus, for unknown reasons, oligodendrocytes may be hypersensitive to perturbations in tRNA biology. Leukodystrophies associated with oligodendrocyte deficits and hypomyelination are known to result when a number of tRNA metabolism genes are mutated. Oligodendrocytes are specialized cells that confer neuronal myelination in the central nervous system.
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