Large-scale mapping of sequence-function relations in small regulatory RNAs reveals plasticity and modularity

Neil Peterman, Anat Lavi-Itzkovitz, Erel Levine

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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. Here, we use a largescale approach to establish a quantitative map between the sequence of a bacterial regulatory RNA and its efficiency in modulating the expression of its targets. 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. We focus on two small RNAs (sRNAs) in E. coli, DsrA and RyhB, and their regulation of both repressed and activated targets. 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. A core of these interactions supports a model where specificity can be enhanced by a rigid molecular structure. Both sRNAs exhibit a modular design with limited cross-interactions, dividing the requirements for structural stability and target binding among modules.

Original languageEnglish
Pages (from-to)12177-12188
Number of pages12
JournalNucleic Acids Research
Volume42
Issue number19
DOIs
StatePublished - 29 Oct 2014
Externally publishedYes

Bibliographical note

Publisher Copyright:
© The Author(s) 2014.

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