Abstract:
:Ribosome profiling is a widespread tool for studying translational dynamics in human cells. Its central assumption is that ribosome footprint density on a transcript quantitatively reflects protein synthesis. Here, we test this assumption using pulsed-SILAC (pSILAC) high-accuracy targeted proteomics. We focus on multiple myeloma cells exposed to bortezomib, a first-line chemotherapy and proteasome inhibitor. In the absence of drug effects, we found that direct measurement of protein synthesis by pSILAC correlated well with indirect measurement of synthesis from ribosome footprint density. This correlation, however, broke down under bortezomib-induced stress. By developing a statistical model integrating longitudinal proteomic and mRNA-sequencing measurements, we found that proteomics could directly detect global alterations in translational rate caused by bortezomib; these changes are not detectable by ribosomal profiling alone. Further, by incorporating pSILAC data into a gene expression model, we predict cell-stress specific proteome remodeling events. These results demonstrate that pSILAC provides an important complement to ribosome profiling in measuring proteome dynamics.
journal_name
Cell Systjournal_title
Cell systemsauthors
Liu TY,Huang HH,Wheeler D,Xu Y,Wells JA,Song YS,Wiita APdoi
10.1016/j.cels.2017.05.001subject
Has Abstractpub_date
2017-06-28 00:00:00pages
636-644.e9issue
6eissn
2405-4712issn
2405-4720pii
S2405-4712(17)30180-1journal_volume
4pub_type
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