RT Journal Article
SR Electronic
T1 Massive Phenotypic Measurements Reveal Complex Physiological Consequences of Differential Translation Efficacies
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 209098
DO 10.1101/209098
A1 Arkin, Adam Paul
A1 Cambray, Guillaume
YR 2017
UL http://biorxiv.org/content/early/2017/10/25/209098.abstract
AB Control of protein biosynthesis is at the heart of resource allocation and cell adaptation to fluctuating environments. One gene’s translation often occurs at the expense of another’s, resulting in global energetic and fitness trade-offs during differential expression of various functions. Patterns of ribosome utilization—as controlled by initiation, elongation and release rates—are central to this balance. To disentangle their respective determinants and physiological impacts, we complemented measurements of protein production with highly parallelized quantifications of transcripts’ abundance and decay, ribosome loading and cellular growth rate for 244,000 precisely designed sequence variants of an otherwise standard reporter. We find highly constrained, non-monotonic relationships between measured phenotypes. We show that fitness defects derive either from protein overproduction, with efficient translation initiation and heavy ribosome flows; or from unproductive ribosome sequestration by highly structured, slowly initiated and overly stabilized transcripts. These observations demonstrate physiological impacts of key sequence features in natural and designed transcripts.