Translation initiation is often over-activated in cancer cells, however, this over-activation does not favour mRNAs equally. In fact it seems translation over-activation favours mRNAs that promote tumourgenesis and tumour progression. Santhanam et al. in PLoS ONE recently took a look at what general mRNA structural characteristics determine translational activity in cancer cells with over-activated translation initiation. Previously lots of focus has been on the influence of secondary structure and length of the 5'UTR as this has been demonstrated to influence 'translatability'. With new information about microRNAs binding to the 3'UTR to influence translation, an unbiased approach to evaluate their relative influence seems like a very good idea. The methods in this work essentially involved comparing microarray analysis of cell lines with over-activated translation initiation and those without. In each cell line the translational activity of each message was determined by quantification of the percentage of the message that was being actively translated. Then they looked for commonalities in the sequence of the mRNAs that are specifically translationally activated by translational over-activation. (probably using computers) :) Massive data set and unbiased approach = pretty convincing coorelations (we're talking p values of 10E-6)
Here is what cancer cells look for in a potentially translatable mRNA:
1. GC rich 3'UTR
2. secondary structure involving sequences JUST before the start codon and JUST after the stop codon. These results are more striking for the 3'UTR.
3. Short 3'UTRs
4. No microRNA target sites. Indeed the presence of predicted microRNA target sites was negatively coorelated with translational over-activation. (with some exceptions)
The take home message is, somewhat surprising, that the 5'UTR is less correlated with effects on translation over-activation relevant to cancer than the 3'UTR.