Similar to a light switch, riboswitches determine which genes turn on and off.
The researchers at the University at Albany and the University at Northwestern University discovered that one part of the RNA invades another part, and that the structure can rapidly and dramatically change. This mechanism appears to switch genetic expression from on to off.
The researchers made this discovery by watching a simulation of a riboswitch up close and in action. Affectionately called R2D2, the new simulation modelsRNA in three dimensions as it binding to a compound, communicating along its length and folding to turn a gene.
The findings could have implications for the design of successful drugs to treat illness and disease.
The study is described in a new paper published today in the journal Nucleic Acids Research, which has designated it as a breakthrough article.
Julius B. Lucks, who co-led the study, said that they found a strand displacement mechanism in other types of RNA.
Lucks is a professor of chemical and biological engineering at the McCormick School of Engineering and a member of the Center for Synthetic Biology. Alan Chen is an associate professor of chemistry at the University of Albany.
R2D2 is a groundbreaking approach.
Every time a gene is expressed in a cell, researchers know very little about the process. Lucks and Chen published a paper in the journal Molecular Cell last year that showed how R2D2 works.
R2D2 uses a technology platform developed in Lucks lab to capture data related to the folding of the RNA. Computational tools are used to mine and organize the data, revealing points where the RNA folds and what happens after it folds. The data was inputted into computer models by a former student of Lucks.
The R2D2 approach combines experimental data on RNA folding at the nucleotide level with predictions at the atomic level to create a simulation of folding in ultra-fast motion, according to Dr. Francis Collins.
Communication long-distance.
The new movies show a riboswitch from a common bacterium found in soil.
There are two basic parts to riboswitches. A part is bound to a compound. Depending on how the compound is bound, the second part causes the RNA to fold into a shape that allows it to control the expression of genes. The Bacillus subtilis is different from the other riboswitches.
The bound molecule can cause large functional changes if it is separated by a long distance. It has been a mystery.
The riboswitch likely communicated downstream through the strand displacement mechanism. The strand exchange process causes structural switch between "on" and "off" states.
Optimizing for drugs.
The stage is set for the riboswitch to perform useful tasks, according to Lucks. The switch could be used for synthetic biology-based diagnostics in the presence of an environmental contaminant. By studying this riboswitch, researchers will learn lessons that could lead to new approaches to create drugs or classes of antibiotics.
Many diseases are caused by something going awry at theRNA level.
More information: Luyi Cheng et al, Cotranscriptional RNA strand exchange underlies the gene regulation mechanism in a purine-sensing transcriptional riboswitch, Nucleic Acids Research (2022). DOI: 10.1093/nar/gkac102Computationally reconstructing cotranscriptional RNA folding from experimental data reveals rearrangements of non-native folding intermediates. There is an article in the journalmolcel.2020.12.017.
Journal information: Nucleic Acids Research , Molecular Cell Citation: Unprecedented videos show RNA switching 'on' and 'off' (2022, March 28) retrieved 28 March 2022 from https://phys.org/news/2022-03-unprecedented-videos-rna.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
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