Importance Of The M(1)G37 Modification And 32-38 Pairing In Trna(Pro)(Ccg) On Decoding And Trna Stability

The ribosome is a complex and highly conserved molecular machine that is responsible for cellular protein synthesis (translation) in all three domains of life. During translation, the ribosome decodes the mRNA sequence three nucleotides at a time (i.e. in a universal triplet reading code) with extreme precision to ensure accurate protein expression that is critical for cellular growth and function. However, it remains unclear how the ribosome maintains, or deliberately deviates from, this three-nucleotide mRNA reading frame. Since the mRNA frame directly corresponds to the resulting protein sequence, the molecular mechanism of both frame maintenance and programmed frameshifting or frame dysregulation is an important question of the Central Dogma. While frameshifting events have been attributed to multiple factors, tRNAs alone can cause the ribosome to shift into noncanonical mRNA reading frames. We previously demonstrated that certain tRNA modifications and insertions alter how the ribosome decodes the mR...