Document Type

Article

Publication Date

5-3-2016

Publication Title

Cell Reports

ISSN

2211-1247

Volume

15

Issue

5

First Page

1100

Last Page

1110

DOI

http://dx.doi.org/10.1016/j.celrep.2016.03.087

PubMed ID

27117410

Abstract

Riboswitches are mRNA elements regulating gene expression in response to direct binding of a metabolite. While these RNAs are increasingly well understood with respect to interactions between receptor domains and their cognate effector molecules, little is known about the specific mechanistic relationship between metabolite binding and gene regulation by the downstream regulatory domain. Using a combination of cell-based, biochemical, and biophysical techniques, we reveal the specific RNA architectural features enabling a cobalamin-dependent hairpin loop docking interaction between receptor and regulatory domains. Furthermore, these data demonstrate that docking kinetics dictate a regulatory response involving the coupling of translation initiation to general mechanisms that control mRNA abundance. These results yield a comprehensive picture of how RNA structure in the riboswitch regulatory domain enables kinetically constrained ligand-dependent regulation of gene expression.

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