Adapting an approach commonly used by immunologists, the team was able to color-code individual particles within cells using antibodies and then sort them by color. They used RNA sequencing to identify which RNAs were associated with which particles. A quick biology review: Cells build proteins using instructions encoded in DNA. Those DNA sequences are transcribed into mRNA inside the cell nucleus. These messenger RNA then move out into the cytoplasm where they are translated into a useful protein. The new study demonstrated that where in the cytoplasm this translation step happens isn't random, and that there's an underlying logic or "code" that directs mRNAs to specific neighborhoods within the cell. Through a painstaking series of experiments, the research team was able to show that mRNAs of different lengths and shapes tend to gravitate to specific neighborhoods. And that if you intervene to redirect them to a different location, it can have a profound impact on the amount of protein that gets produced and on the protein's function.

 

Cracking the code for how mRNA localize to different locations revealed some surprising findings. It turns out that the tail is essential for partnering with RNA-binding proteins so that, together, the mRNA goes to the correct translation region within the cell. The really surprising finding was that the RNA-binding proteins actually play a secondary role rather than a primary role in the process. Several MYC protein complexes were only formed when MYC mRNA was translated in the granules and not when it was translated in the cytosol. The results show there's an important biological relevance to these neighborhoods, even when only about 20% of mRNAs get translated in the TIS granules.