Outside the Nucleus: Cytoplasmic DNA Synthesis linked to Degeneration.

        In the article “Human Cells Can Synthesize DNA in Their Cytoplasm” scientists have reports which have identified mammalian DNA to be found in the cytoplasm when they would usually find foreign DNA there. However when complementary DNA (cDNA) was discovered to have been synthesized from RNA scientists were baffled. This is due to the fact that because of the mechanism in which they insert copies of themselves into the genome occurs in a copy and paste pattern where such an event usually occurs in the nucleus. Studying cDNA found in the most abundant retrotransposon Alu, when concerning degenerative eye diseases the cDNA of Alu in humans is found to be synthesized in the cytoplasm. 

        Based on previous studies with Alu and other retrotransposons, the way in which reverse transcription occurs in the nucleus considers that it needs a short nucleic sequence, and primer bound to the RNA template to start. However for Alu to undergo reverse transcription in the cytoplasm the nucleic sequence is not present. Which led to the hypothesis that the RNA folds on itself which is also known as self-priming. The cytoplasmic discovery also correlated that age-related macular degeneration (AMD) is due to the cell death of the retinal pigment epithelium because of the abundance of Alu. Since learning of cDNA synthesized Alu connection to the eye degenerative disease it has also been linked to causing inflammation. To manage AMD scientists developed Alu inhibitors which would control Alu accumulation and even treat other infections. The drug which was developed NRTI is said to prevent inflammation and intercept transcription. Since the current drug is in clinical trial it could help cure a degenerative disease which ultimately leads to permanent blindness. With the development that DNA synthesis can  occur without a nucleic sequence to start transcription it is possible to learn that this mechanism could be responsible for other diseases that currently do not have treatments or most effective treatments. 

Change Occurring in the Cytoplasm

 

The article Squid Edit Their Genetic Material in a Uniquely Weird Place details an important discovery of an ability that a certain individual can do unlike most known animals. The Longfin inshore squid or the Doryteuthis pealeii is the only known animal to be able to edit their mRNA or messenger RNA outside of the nerve cell nucleus. Generally most animals are able to make edits to their RNA but do so rarely and when they do they are done within the nucleus and then exported out. The unique ability that the Longfin inshore squid has is that it can do its RNA edits in the cytoplasm.

    The method in which the squid edits their RNA is similar to how CRISPR is used to make edits in DNA. CRISPR has allowed for DNA sequences to be modified to correct genetic defects that are threatening and even aid in the genetic modification of crops. But unlike editing DNA which happens to be a bit tricky because errors are permanent, editing the RNA isn't as dangerous and unlikely to repeat because RNA is broken down. Studies show that it is possible that squid is able to edit their RNA in both the nerve cells (neurons) that send signals to the brain and throughout the body and in the cytoplasm at the same time.With this new discovery it's important to consider this as a possible to track to discovering how to develop therapies that would be useful to treat chronic conditions. While more research is needed it would benefit the medical community to find other alternatives to treat chronic conditions besides just prescribing medications. 

Studying Squids to Help Find a New Way of Pain Relief

 

    Some organisms can make edits or changes to their genetic material. Most organisms perform this function of editing their RNA in the nucleus and then are sent out to the rest of the cell. Squids however, discovered a way to change up the genetics of their cytoplasm. This is a first for animals editing genetic information outside of the nucleus. Studying how the squid species perform this odd function could aid in medical research. A study on this matter was conducted by extracting cytoplasm for a squid's axons after they discovered that mRNA editing proteins were found in the squids nerve cells. The protein ADAR2 was found to be located in both the squids cytoplasm and the nucleus of neurons. This would explain why these squids were able to change the genetic material in the cytoplasm. 

I believe that these findings are important because they could help scientists find a way to reduce long term pain in human nerve cells. I think manipulating the genetics of the mRNA can help find new advances in modern medicine. Axon dysfunction in humans is linked to neurological disorders, these new findings and studies could potentially also help humans therapeutically.

https://www.sciencenews.org/article/squid-edit-their-genetic-material-uniquely-weird-place

https://www.sciencedaily.com/releases/2020/03/200323125629.htm#:~:text=In%202015%2C%20Rosenthal%20and%20colleagues,produced%20in%20the%20nervous%20system.