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Updated: Oct 11, 2025

Genome-wide Quantification of Translation in Budding Yeast by Ribosome Profiling
Published on: December 21, 2017
Ribosome profiling reveals novel regulation of C9ORF72 GGGGCC repeat-containing RNA translation
Heleen M van 't Spijker1, Emily E Stackpole1, Sandra Almeida2
1Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts 01605, USA.
Abstract:
GGGGCC (G repeat expansion in the first intron of C9ORF72 causes amyotrophic lateral sclerosis and frontotemporal dementia. Repeat-containing RNA is translated into dipeptide repeat (DPR) proteins, some of which are neurotoxic. Using dynamic ribosome profiling, we identified three translation initiation sites in the intron upstream of (G2) repeats; these sites are detected irrespective of the presence or absence of the repeats. During translocation, ribosomes appear to be stalled on the repeats. An AUG in the preceding C9ORF72 exon initiates a uORF that inhibits downstream translation. Polysome isolation indicates that unspliced (G2) repeat-containing RNA is a substrate for DPR protein synthesis. (G2) repeat-containing RNA translation is 5' cap-independent but inhibited by the initiation factor DAP5, suggesting an interplay with uORF function. These results define novel translational mechanisms of expanded (G2) repeat-containing RNA in disease.
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