Protein trans-activation of ribosomal frameshifting: a new paradigm in gene expression

The macromolecular machine responsible for protein synthesis, the ribosome, translates messenger RNAs (mRNAs) by decoding triplets of bases (codons) as amino acids.The ribosome sticks to the triplet code (the reading frame) until it reaches a stop signal, at which point the completed protein is released. However, many viral and cellular mRNAs have embedded signals that instruct the translating ribosomes to change reading frame, frameshifting at a defined position and to continue translation in an overlapping coding frame. These are not errors as the frameshift products have distinct biological functions. The mRNA signals that induce frameshifting include a structured RNA, referred to as the stimulatory RNA, that blocks ribosome progression until a frameshift takes place. 

We have recently identified examples of viral frameshift signals that lack such RNAs and instead require the participation of viral and cellular proteins to be active. Such trans-activation of frameshifting by proteins is completely novel. We will investigate how these proteins promote frameshifting by analysing their structure and function. 

This work promises to provide new insights into ribosome function and gene expression strategies.