Fastest-known RNA switches may help combat HIV

Washington: Scientists have discovered the smallest and fastest-known molecular switches made of RNA which can act as prime targets to develop drugs to combat HIV. Over the past decade, researchers have determined that most of the Deoxyribonucleic acid (DNA) in our cells is used to make Ribonucleic acid (RNA) molecules, that RNA plays a central role in regulating gene expression, and that these macromolecules act as switches that detect cellular signals and then change shape to send an appropriate response to other biomolecules in the cell. [caption id=“attachment_483274” align=“alignleft” width=“380”]  Representative image. Getty Images[/caption] While RNA’s switching function has been well-documented, researchers from the University of Michigan have found a new class of switches that are significantly smaller and orders of magnitude faster than the other known class of RNA switches. Researcher Hashim Al-Hashimi called these short-lived structures, which were detected using a new imaging technique developed in his laboratory. “We’re finally able to zoom in on these rare, alternative forms of RNA that exist for just a split second and then are gone,” Al-Hashimi said. “These things are so difficult to see because they exist for roughly 1 per cent of the time and for only a microsecond to a millisecond,” Al-Hashimi said. In biology, a molecule’s three-dimensional shape determines its properties and affects its function. RNA molecules are made of single chains that can remain stretched out as long threads or fold into complex loops with branching, ladder-like arms. The micro-switches described by researchers involve temporary, localised changes of RNA structure into alternativeforms called excited states. The structural change is the switch: the shape shift transmits biological signals to other parts of the cell. “These excited states correspond to rare alternative forms that have biological functions. These alternative forms have unique architectural and chemical features that could make them great molecules for drugs to latch onto. In some sense, they provide a whole new layer of drug targets,” Al-Hashimi said in a statement. Researchers looked at transient structural changes in three types of RNA molecules. Two of the RNAs came from the Human immunodeficiency virus (HIV) that causes AIDS and are known to play a key role in viral replication. The third is involved in quality control inside the ribosome, the cellular machine that assembles proteins. The newly found excited states of all three of these RNAS provide potential targets for drug development: antiviral drugs that would disrupt HIV replication and antibiotics that would interfere with protein assembly in bacterial ribosomes, researchers said. The study was published in the journal Nature. PTI