The mRNA landscape at yeast translation initiation sites

Here, we analyze mRNA secondary structure using the folding predictions of the RNAfold algorithm. We present a method for analyzing these results using a rank-ordering approach to assess the overall degree of predicted secondary structure in a given region of mRNA. In addition, we used a modified version of the algorithm that makes use of only a subset of the standard version's output to incorporate base-pairing polarity constraints suggested by the ribosome scanning process. These methods were employed to study the TISs of 1735 genes in Saccharomyces cerevisiae. Trends in base composition and base-pairing probabilities suggest that efficient translation initiation and high protein expression are aided by reduced secondary structure upstream and downstream of the TIS. However, the downstream reduction is not observed for sets of TISs with nucleotide sequence contexts unfavorable for translation initiation, consistent with previous suggestions that secondary structure downstream of the ribosome can facilitate TIS recognition.