New Study Finds The Impact Of RNA Modification On Learning And Memory

Genetic Material of our body is the primary factor that influences the growth, functioning and development of our body. Both the RNA as well as the DNA has their fair share of work that reflects on the overall outlook of our body functions. But, are the claims surrounding the impacts of RNA modification on learning and memory true?

A new study (R) conducted by the researchers of the University of Chicago Medical Center have found that even the slightest of the modification in the RNA can actually positively influence the process of learning and memory formation.

The RNA in our body is responsible for carrying information encoded in the DNA itself to carry out the seamless protein production that is primarily responsible for the ongoing activities inside the cell. While the process might often seem streamlined, for the most part, it always isn’t. It has been found that the impacts of chemical interactions can actually end up causing modifications to the DNA and the RNA altering the gene expression in the process. These significant epigenetic or epitranscriptome changes have profound impacts on the immune system function, obesity, risks of cancer and even with the development of the nervous system.

Majority of the times, the impacts on these kinds of molecules mainly occur because of the process of methylation in which a number of chemical compounds end up adding methyl groups to the DNA and the RNA molecule. These protein compounds which add the methyl group while the other variant is known as the eraser. For the impactful biological impact with the methylation process, it is necessary for the reader proteins to identify and bind to the necessary sites.

For the most part, it is witnessed that the common methylation process is that of the messenger RNA (mRNA) known as the N6-methyladenosine (m6A). It is predominantly found in the nervous system and is responsible for coordinating the neural functions, working through the reader proteins present in the YTH family of proteins.

In this conducted study by the researchers from the University of Chicago, it was found that Ythdf1, which is predominantly a part of the YTH family of proteins have an important effect on the process of learning and memory formation. The researchers made use of the CRISPR/Cas9 gene editing tools to get rid of the Ythdf1 in the mice, they were actually able to demonstrate how it impacts the translation process of the m6A modified messenger RNA which has direct influence on the learning and memory of an individual.

Chuan He, PhD, the John T. Wilson Distinguished Service Professor of Chemistry, Biochemistry and Molecular Biology at UChicago and one of the senior authors of the study stated saying that this was actually quite an impactful way to open up the doors for further understanding of the factors the affect the process of learning as well as memory.

Upon extensive research, they found quite a starking difference between the long term memory as well as the learning between that of the normal as well as the knockout mice advising the fact that the process of m6A methylation does play an extensive role through the Ythdf1.

The researchers found that mice did express more of the Ythdf1 in the hippocampus region of the brain which is primarily associated with the spatial learning and memory. In order to test out the degree of efficiencies, the researchers conducted an array of study on the normal mice as well as the one without the Ythdf1 to test out the abilities of them to learn with the absence of it.

In one of the situations known as the Morris Water maze, in which the mice are made to stand on a platform in a water filled tank with several practices to test out the stability, it was found that the normal mice with everything intact was able to learn the process better and keep themselves stable on the platform. On the other hand, the one without the Ythdf1 was not able to efficiently do the same.

Apart from that, the researchers even conducted a test for the contextual fear and associated memory in the mice. It was found that the normal mice did express an expression of fear when they were put back in the same cage where the electrical impulses were administered. This proved to be a better showcase of the contextual memory.

In order to test out the impacts of the altered RNA, the knockout mice was then again injected with a viral strain of the Ythdf1 and almost instantly, the impacts were reversed and it positively influenced the performance on memory as well as learning almost immediately and that too by quite a substantial amount.

The researchers further tested out the response of the cultured mouse neurons in the lab itself. They found that when the neurons of the normal mice were stimulated, it stimulated the production of new proteins which was comparatively a lot lesser in that of the knockout mice.

Hailing Shi, a graduate student in He’s lab, who led the new study stated that it is quite fascinating to watch how the production of protein can amplify based on the neuronal stimulus which further contributes to controlled translation. He further stated saying that the entire process is a stimulation dependant upregulation which does make sense.

While this current study just points out the correlation between Ythdf1, RNA modifications and learning and memory, the realm of functionality might actually be even more pronounced. It is not just limited to the realms of one side of cognitive abilities but might be impactful in some other aspects too which will definitely need more studies and research.