Large-scale mapping of sequence-function relations in small regulatory RNAs reveals plasticity and modularity.
Bottom Line: Two decades into the genomics era the question of mapping sequence to function has evolved from identifying functional elements to characterizing their quantitative properties including, in particular, their specificity and efficiency.Our approach generalizes the sort-seq method, introduced recently to analyze promoter sequences, in order to accurately quantify the efficiency of a large library of sequence variants.In addition to precisely identifying functional elements in the sRNAs, our data establish quantitative relationships between structural and energetic features of the sRNAs and their regulatory activity, and characterize a large set of direct and indirect interactions between nucleotides.
Affiliation: Department of Physics and FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.Show MeSH
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Mentions: For RyhB-sodB, our sRNA mutant library included data for 11 910 pairs of mutations, presented in Figure 6. Because the additive model provided a good approximation of repression efficiency for the vast majority of variants with two mutations (98% of measurements fall within 2-fold of the additive prediction), most pairs of mutations interacted weakly if at all. However, a small fraction of measurements showed strong interactions. Interactions that we consider both strong and statistically significant are presented in Figure 6A and B, and the distribution of all measured IS is plotted in Figure 6C.
Affiliation: Department of Physics and FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.