Understanding mRNA Transport Pathways to Help Avoid Disease
Carly Cannon (11 AM Micro) found an article about one problem faced by eukaryotic cells, due to their larger size. That is, how can messenger RNA transcripts move from their site of synthesis at the DNA molecule to their site of use at ribosomes? I was particularly excited to see this this article, as my graduate dissertation dealt with mRNA transport in the model organism Saccharomyces cerevisiae. Here is Carly’s summary:
Dr. Graydon B. Gonsalvez is a cell biologist at the Medical College of Georgia at Georgia Regents University who was recently given a $1.4 million dollar grant from the National Institute of Health to study the journey of mRNA to where it ultimately needs to be. The cell that Dr. Gonsalvez used as a model to study the movement of mRNA is Drosophila oocyte. Drosophila oocyte is a cell that is only used in embryonic patterning because of the rapid rate of division of the early cells. They use mRNA transport to make sure all of the new, rapidly dividing cells are able to receive the mRNA transcripts they need to develop into different cells. The mRNA transport process of Drosophila oocyte cells is similar as in other eukaryotic cells, but the cell is much larger which makes it a good model to study. An oocyte has to make it to the correct localized area carrying the mRNA transcript, or it will not function properly. This is the same with the mRNA inside the cell, the motor protein must make it to its specific location with the mRNA in order for it to function properly. By studying the oocyte cell and seeing how being able to reverse its tracks is needed to get to the localized area, it will help them understand how it is needed in a normal cell also.
This idea of mRNA being able to reverse its tracks to function came when the scientists noticed 2 motor proteins side by side in the cell that would go in opposite directions. When one motor protein was carrying the mRNA to a location, they removed the idle protein that was sitting next to it to begin with. This caused the mRNA that was already en-route to not be able to make it to its specific location because it would not be able to change directions. They determined from this that if the mRNA can only go in one direction, it will not be able to change tracks when it runs into an obstacle so that obstacle will stop the mRNA from going on.
There are many more topics on the tracks of mRNA that need to be studied which is the reason for the $1.4 million dollar grant that Dr. Graydon B. Gonsalvez received. One of the big issues in the study is figuring out how the motor proteins know which mRNA they need to transport because not all mRNA are localized. Their original idea is the idea of a “zipcode” for where each mRNA needs to go, but how the motor proteins know where to take the mRNA that are not localized is still an issue with this idea.
The theory behind Fragile X syndrome or “mental retardation” (a genetic condition that causes intellectual disability, behavioral and learning challenges and varied physical characteristics) is that one or more of the motor proteins that should be bound to the mRNA to transport it to its localized area are missing. This results in the mRNA not transferring the information to that area, causing decreased intellectual ability and other challenges.
The hope behind this expensive research is to understand what defects in motor proteins lead to these diseases and why these defects occur so one day they can stop these defects and eliminate these diseases.