Detection of Global and Gene Specific Translational Control Signals in mRNAs
Chris M Brown1, Grant Jacobs2, Mark Dalphin and Peter Stockwell
1chris.brown@otago.ac.nz, University of Otago; 2gjacobs@bioinfotools.com, Bioinfotools
We wish to detect signals in mRNAs that may influence their translation. We are most interested in signals that affect a mRNA's stability and localisation, and promote its efficient translation. Often such signals are located in particular regions of the mRNA. For example, signals that influence initiation are usually located near to the initiation codon, or surprisingly, far away in the 3' UTR. Therefore, we have extracted relevant regions from Genbank sequences on a species by species basis. After reducing redundancy, summary statistics are derived for each species and mRNA. The database also includes data for known signals, motifs, or structures in RNAs. However, this functional information is limited by the lack of biological data about such motifs, and the difficulty of describing them in terms of primary and secondary structure. This data is available publicly in the TransTerm database (transterm.otago.ac.nz).
We first analysed regions around termination codons and discovered strong biases in base usage particularly in the position following the stop codon. These bases were subsequently shown to affect the efficiency of termination in E. coli, S. cerevisiae and human cells in publications by several groups.
This analysis has been extended to initiation contexts and we have found that several species may utilise unusual methods of initiation codon selection. These observations have not been experimentally tested yet.
Comparisons between the 3'UTRs of mammalian species have for some genes revealed striking similarity. The overall identity for these sequences between mouse and human is about 69%. However some genes show 91-96% identity over long 3' UTRs (> 2000 bases) or in 100 base-pair windows. These highly conserved regions (HCR) or conserved non-coding Sequences (CNS) may have functional significance. We are currently investigating these observations with in vivo assays.