In a recent Cell Reports paper, Dr. Bin Tian and team revealed a mechanism that has far-reaching implications in development and diseases, including immunity and cancers.
The lab studies RNA biology to understand just how gene expression is regulated at the RNA level.
The genetic code of DNA to RNA and proteins is fine-tuned at different stages. Most control mechanisms take place after RNA is made.
Tian and colleagues focus on a mechanism called alternative polyadenylation (APA) that modifies the tail end of RNA sequences to generate multiple messenger RNAs from the same gene, which scientists call isoforms. This dramatically increases the complexity of our genome, so that fewer genes are needed to encode all the proteins a cell needs.
Though this mechanism affects more than half of human genes, its significance was poorly understood.
However, the lab uncovered the role APA plays in facilitating protein production in certain sites within the cell where those proteins are most needed.
“When mRNAs leave the nucleus and move to the cytoplasm, they need to be properly directed to reach the appropriate site of protein translation,” said Dr. Tian. “The cytoplasm is a huge space for an RNA molecule: For comparison, imagine entering a baseball stadium and needing directions to reach your seat.”
Researchers discovered that APA directs certain messenger RNAs to the endoplasmic reticulum (ER), a network of tubes that build, package and transport proteins. They also found that specific sequences and structures within the messenger RNAs determine their potential to undergo APA and ultimately associate with the ER.
These mRNAs tend to encode for signaling proteins, which help cells communicate with each other by sending, receiving, and processing signals in response to changes in the environment.
Dr. Tian and his team hypothesize that association with the ER anchors certain mRNA isoforms in specific cellular locations where important signaling events happen, making the whole process more efficient.
“According to our model, the ER would serve as a scaffold to keep proteins ‘on hand’ where they are most needed,” said Tian. “This would provide a platform for signaling events to happen effectively at the right place in the cell.”
This study has far-reaching implications in development and disease, including immunity and cancer. The Tian lab is exploring approaches to regulate APA as a new therapeutic modality.