A New Start for Protein Synthesis

Recent technical advances have led to the accumulation of vast amounts of DNA sequences, highlighting the importance of understanding how the information in DNA is translated into amino acids and proteins. To decipher this information, the cell first transcribes a "coding" segment of DNA into messenger RNA (mRNA). Next, the ribosome decodes the mRNA in blocks of three consecutive nucleotides, or codons, that each specify an amino acid. But, how does the ribosome know where to start reading on the mRNA? To ensure faithful translation, and thereby yield a functional protein, cells restrict translation initiation to AUG codons that specify the amino acid methionine (Met). In mammals and other eukaryotic cells, translation typically initiates at the AUG codon closest to the beginning of the mRNA. But on page 1719 of this issue, Starck et al. (1) show that in addition to the canonical AUG-methionine initiation pathway, CUG-leucine can also be used to initiate protein synthesis. Protein synthesis that does not initiate with methionine is used by the mammalian immune system to process antigen. Protein synthesis that does not initiate with methionine is used by the mammalian immune system to process antigen.