Scientists Create Video of HIV RNA

One of the most maddening aspects of working at the nanoscale is you there just isn't any way to see what is going on at a scale so small that comparisons are made on how many thousands of the things being observed will fit in a single human hair. That is, until now, according to a paper going to press December 20 in the journal Nature.

A research group at the University of Michigan led by Hashim al-Hashimi, Associate Professor of chemistry and associate researcher in biophysics, has devised a means of taking 3-dimensional pictures of ribonucleic acid (RNA) while it as at work. The RNA used in the study was one of those critical for the replication of HIV, which causes AIDS.

RNA is a workhorse within the inner workings of a cell, regulating gene expression, carrying information between the nucleus and ribosomes and mitochonria, and controlling the construction of the various proteins used within a living cell. It also serves as the 'sensor' for each cell, and triggers the cell into action when key triggers, such as an attack by a virus, occurs.

Most disease viruses, including the human immunodeficiency virus (HIV) which causes acquired immune deficiency syndrome (AIDS), are comprised of RNA being carried around inside a protein sheath, and insert their RNA into a cell to take it over - and kill it.

RNA works by first sensing another chemical in its vicinity, then radically changing its shape, creating different energy boundaries along its length. Understanding how and when the RNA changes shape in response to its environment is critical to understanding the overall function.

Hashimi's research has extended previous modeling techniques, which relied solely on observational data and created animations that were only nanoseconds-long, to a millisecond, a several thousand-fold increase and making practical the use of such modeling.

Using a unique application of nuclear magnetic resonance imaging (NMR), Hashimi's team created their 'nano-video' by observing the various legs of one segment of the TAR segment of RNA from a strain of HIV. The TAR sequence is critical for the replication of the HIV virus and subsequent development of AIDS as more and more cells become infected. By understanding how, where, and when the viruses RNA changes while it works gives scientists a tool that could lead to developing compounds to disrupt that process, killing the virus.

Coauthors on the Nature paper are graduate students Qi Zhang and Andrew Stelzer and undergraduate student Charles Fisher. The researchers received funding from the National Institutes of Health.