In a study published in the journal Cell, researchers have uncovered a protein responsible for recognizing a chemical tag that determines how an RNA sequence turns out.
RNA leads to many things after DNA transcription – most commonly protein production – but what a lot of people don't realize is that the molecules also have the ability to alter gene expression. The chemical tag m6A was identified over 40 years ago in RNA sequences and has been believed to influence several important processes. However, it was unclear what was reading these tags, which made it possible to carry out the instructions they contained.
Claudio Alarcón – a research associate in the lab of Sohail Tavazoie – was able to identify a "reader" protein, which highlights implications for the normal functions of cells and for disease. Tavazoie is the head of the Elizabeth and Vincent Meyer Laboratory of Systems Cancer Biology at Rockefeller University.
Called HNRNPA2B1, the reader protein was shown to have the ability to recognize m6A tags on RNA destined to either get spliced to be properly turned into protein or trimmed to become microRNAs. MicroRNAs are tiny RNA molecules that turn down gene activity.
After the reader protein recognizes the m6A tags, HNRNPA2B1 recruits cutters that will further trim and process RNA molecules. The researchers said that additional studies are needed to see how HNRNPA2B1 interacts with proteins responsible for RNA splicing.
HNRNPA2B1 was believed to be the reader protein because it was observed frequently binding to the same sites where m6A tags attach. To find out what the protein was doing there, the researchers reduced levels of HNRNPA2B1 in cells.
In the cells with reduced levels of the protein, it was found that microRNA expression shifted, with microRNAs dramatically reduced. RNA for splicing was also examined and found to have undergone dramatic changes as well.
So far, HNRNPA2B1 is the first reader protein identified in relation to m6A. Experiments suggest that there are more, and identifying them will be one of the next goals for RNA researchers.
"The discovery of this new m6A reader has ramifications for a broad range of processes," said Alarcón, adding that RNA splicing determines which proteins are made available within cells and microRNA abnormalities have been associated with diseases.
Saeed Tavazoie, Xuhang Liu, Hyeseung Lee and Hani Goodarzi are the other authors who worked on this study.
