High-level ribosomal frameshifting directs the synthesis of IS150gene products

Abstract

IS150 contains two tandem, out-of-phase, overlapping genes, ins 150A and ins 150B, which are controlled by the same promoter. These genes encode proteins of 19 and 31kD, respectively. A third protein of 49kD is a transframe gene product consisting of domains encoded by both genes. Specific −1 ribosomal frameshifting is responsible for the synthesis of the large protein. Expression of ins 150B also involves frameshifting. The IS 150 frameshifting signals operate with a remarkably high efficiency, causing about one third of the ribosomes to switch frame. All of the signals required for this process are encoded in a 83-bp segment of the element. The heptanucleotide A AAA AAG and a potential stem-loop-forming sequence mark the frameshifting site. Similar sequence elements are found in −1 frameshifting regions of bacterial and retroviral genes. A mutation within the stem-loop sequence reduces the rate of frameshifting by about 80%. Artificial transposons carrying this mutation transpose at a normal frequency, but form cointegrates at a ≈100-fold reduced rate.