A dynamic RNA loop in an IRES affects multiple steps of elongation factor-mediated translation initiation

Many viruses store their genetic information in the form of strands of ribonucleic acid (RNA), which contain building blocks called nucleotides. Once inside an infected cell, the virus hijacks the cellular structures that build proteins (called ribosomes), which forces the cell to start making viral proteins. Many RNA viruses manipulate the cell’s ribosomes using RNA elements called Internal Ribosome Entry Sites, or IRESs. In a family of viruses called Dicistroviridae, which infect a number of insects, a section of the IRES RNA binds directly to the ribosome. Proteins called elongation factors then trigger a series of events that lead to the cell starting to make the viral proteins. By mutating the RNA of many different Dicistroviridae viruses that infect a variety of invertebrates, Ruehle et al. have now investigated how a particular loop in the structure of the IRES helps to make cells build the viral proteins. This loop is flexible, and interacts with the ribosome to enable the IRES to move through the ribosome. Mutations that shorten the loop or alter the sequence of nucleotides in the loop prevent the occurrence of two of the steps that need to occur for the cell to make viral proteins. Both of these steps depend on elongation factors. Determining how the entire IRES might change shape as it moves through the ribosome is an important next step, since the ribosome is exquisitely sensitive to the shape and motions of its binding partners.