If you forgot to add the zip code to a letter, would it still reach the correct destination? Eventually it should, thanks to the US Postal Service and the other address information. Cells also need to ensure their messages reach the correct destinations, and a recent paper in Molecular Biology of the Cell reveals that, just like the post office, cells use multiple layers of information to target messenger RNA transcripts (mRNAs) to an important cellular address.
mRNAs relay genetic information from DNA in the nucleus out to the rest of the cell. To read these mRNA messages the cell uses a molecular machine called a ribosome, which decodes the information in an mRNA to construct a chain of amino acids that folds into a protein (this process is called translation). Proteins can do their jobs only in specific cellular locations, so both proteins and mRNAs carry signals that act as the cellular address. One is the signal sequence, which directs proteins to a group of membrane-bound organelles called the endomembrane system . The signal is encoded in the mRNA but only recognized once it is translated by the ribosome into protein. This signal is recognized by the Signal Recognition Particle (SRP), which acts as a molecular postman by bringing that protein (and the mRNA being translated) to the entrance of the endoplasmic reticulum (ER). There are two kinds of proteins that are sent to the endomembrane system by signal sequences. The first are those that are secreted to the outside of the cell (“non-residents”) and the second are those that stay behind to do their job from within the endomembrane system (“residents”). The researchers, Chen et al, were surprised to find that mRNAs encoding non-resident proteins were less likely to be delivered to the ER than those that encode residents, even though both have signal sequences (i.e. correct addresses)! The two different kinds of mRNAs also seemed to be attached to the ER by different mechanisms. This means that in addition to signal sequences, there must be other unknown signals that also direct mRNAs to the ER.
These results indicate that undiscovered signals allow the cell to give higher priority delivery to resident versus non-resident proteins. The authors speculate that this priority might be important during the production of antibodies when we are sick, which requires expansion of the endomembrane system by the resident proteins. These findings will also help scientists to more accurately read mRNA address codes, manipulate the location of genetically engineered proteins, and predict the cellular location of the many proteins whose functions they don't yet understand. The next task is to find these undiscovered signals.
— Cristy Gelling for ASCB’s CellTweet working group