Mechanistic Insights into Cofactor-Dependent Coupling of RNA Folding and mRNA Transcription/Translation by a Cobalamin Riboswitch.

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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Polaski JT,Holmstrom ED,Nesbitt DJ,Batey RT

doi

10.1016/j.celrep.2016.03.087

subject

Has Abstract

pub_date

2016-05-03 00:00:00

pages

1100-1110

issue

5

issn

2211-1247

pii

S2211-1247(16)30393-X

journal_volume

15

pub_type

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