Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway

摘要

Genes are used as templates to create molecules of messenger RNA (mRNA) that contain all the information needed to make a protein. This information begins with a 'start site' and ends with a 'stop site.' The regions of the mRNA outside of the start and stop sites are called untranslated regions. Not all mRNAs are correctly made, and cells combat this problem by detecting and destroying faulty mRNAs before they are translated into protein. One way cells do this is by recognizing and destroying mRNAs that include long untranslated regions, which can indicate that the mRNA might have a stop site too early in its sequence. A key problem with this mechanism, however, is that long untranslated regions also serve important roles in the cell for example, by determining where and when mRNA molecules are read to make protein. How then do mRNAs with long but important untranslated regions escape detection and degradation? Ge et al. have now investigated this question using an approach that allows a 'handle' to be attached to particular RNA molecules. This allows the RNA and any proteins bound to it to be purified away from all other RNAs and proteins in the cell, and the proteins can then be identified by a technique called mass spectrometry. Ge at al. found that mRNAs can recruit a protein called PTBP1 to part of the RNA sequence near the stop site. This prevents an RNA decay protein recognizing and triggering the degradation of the mRNA, even if the mRNA has a long untranslated region. Thus, PTBP1 plays a crucial role in protecting human RNAs with long untranslated regions from destruction by the nonsense-mediated decay pathway. Some viral RNAs are also able to evade decay, and so Ge et al. hypothesize that the virus stole this method for maintaining its RNAs from host cells. A future goal is to understand whether this system works the same way in all cell types or protects different RNAs in different cells.