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Initiation of translation at ambiguous start sites

Elena Mayer (Master Student)

During initiation, the ribosome is tasked to efficiently recognize open reading frames (ORFs) for accurate and fast translation of mRNAs. A critical step is start codon recognition in bacteria, which is modulated by initiation factors, mRNA structure, a Shine Dalgarno (SD) sequence and the start codon itself. Within the E. coli genome, we identified more than 50 annotated initiation sites harboring AUGUG or GUGUG sequence motifs that provide two canonical start codons, AUG and GUG, in immediate proximity. As these sites may challenge start codon recognition, we study if and how the ribosome is accurately guided to the designated ORF, providing the cell with sufficient initiation accuracy.

Figure taken from: Maximilian P Kohl, Maria Kompatscher, Nina Clementi, Lena Holl, Matthias D Erlacher; Initiation at AUGUG and GUGUG sequences can lead to translation of overlapping reading frames in E. coli. 2022 Nucleic Acids Research, 51 (1); 271–289;