Solid State and Structural Chemistry Unit

Indian Institute of Science, Bangalore – 560 012

Dr. Susmita Roy

Affiliation: Rice University


Effect of magnesium in riboswitch regulated gene expression

Date & Time : Monday 16th April, 2018 at 4:00 PM
Venue : SSCU Auditorium
Riboswitches, a class of non-coding RNA elements located in the untranslated 5′
stretch of certain bacterial messenger RNAs (mRNA), have recently been recognized
as important players in controlling bacterial gene expression. The control is often
exerted via the level of cellular metabolites that self-regulate their production,
binding directly to a riboswitch motif on the mRNA that encodes enzymes involved in
their biosynthesis. While gene expression regulation by riboswitches is wide-spread
in bacteria, they are sparsely found in human. Due to their abundance in bacteria
and sophistication of small molecule sensing strategies, in recent times, riboswitch
represents promising drug target for antibiotics. Molecular biology, therefore, seeks
to understand and expand this amazing sensing ability of riboswitches, in accord
with their structural and functional responses under different environmental
conditions. Positively charged metal ion environment is essential to maintain the
structural fold and thus functions of RNA. Among different metal ions, magnesium
is particularly important for the stability of RNA because it can efficiently support a
close assembly of negatively charged phosphate groups in an RNA fold. Here, I will
present my postdoctoral research which aims to develop a structure-based
generalized electrostatic model of RNA, integrated with the essential effects of RNA
ion-atmosphere including counter-ion condensation phenomenon. This model has
spurred new possibilities encouraging us to deal with substantially large length-
scale and long-time scale processes those are associated with complex riboswitch
responses, both in the presence and absence of metabolite under different buffer
conditions. In this spirit, I’ll discuss how magnesium ion-atmosphere pre-organizes
a non-coding RNA triplex that facilitates stable metabolite-binding which, in turn,
regulates the translation initiation process. I will also discuss how one can control
transcription ON-OFF switching in bacteria by tuning the ion-atmosphere of RNA.
All the studies tie together state-of-the-art enhanced sampling molecular
simulations with our newly developed potential and different biochemical