Measuring translation initiation rates is difficult. Gao et al. developed quantitative translation initiation sequencing (QTI-seq), a technique that captures translation initiation sites (TISs) at single-nucleotide resolution in cells and solid tissues, based on dissociating elongating ribosomes from transcripts while preserving the initiating ribosomes. The authors used QTI-seq to profile the effects of amino acid starvation on HEK293 cells and mouse embryonic fibroblasts (MEFs). Starvation-responsive transcripts often displayed multiple TISs, indicating a role for alternative TISs in translation control. In mouse livers, fasting elicited a different response to that in MEFs: the translation initiation of ribosome biogenesis transcripts was not repressed, and that of transcripts encoding components of the proteasome was enhanced. This indicates that a continuous supply of ribosomal proteins is needed in the liver during prolonged fasting, and that the proteasome contributes to cellular amino acid supplies.
References
Gao, X. et al. Quantitative profiling of initiating ribosomes in vivo. Nature Methods http://dx.doi.org/10.1038/nmeth.3208 (2014)
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Zlotorynski, E. Capturing translation initiation. Nat Rev Mol Cell Biol 16, 3 (2015). https://doi.org/10.1038/nrm3928
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DOI: https://doi.org/10.1038/nrm3928