Frederick “Eric” Arnold, PhD, on Investigating MARK3 Polyadenylation and Microtubule Dynamics in ALS Models

“Motor neurons, in particular, have these really long axons. And so you have to make sure that the cargo is being trafficked over these super long distances, including RNAs. That's an aspect of 3-prime untranslated region (3′-UTR) biology that alternative polyadenylation regulates. [In] some other work that's been done, they refer to it as zip codes. So, within the 3′-UTR, you can havemotifs or sequences that will affect whether an RNA is more localized to thecell body, or is being trafficked along axons to these distal regions.”

Cases of amyotrophic lateral sclerosis (ALS) with known genetic causes also make up around 5-10% of ALS cases. Of these cases, the predominant associated genes are SOD1 and C9orf72. New research from University of California – Irvine is examining the TDP-43 protein, and how changes in alternative polyadenylation that are regulated by TDP-43 affect neuronal cells and ALS.The project is headed by Frederick “Eric” Arnold, PhD, postdoctoral scholar.

Arnold discussed the ongoing research during a session at the 2024 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, entitled "Translational research in ALS: Novel Biomarkers and Model Systems" held March 3-6, in Orlando. CGTLive® spoke with Arnold to learn more about the research. He shared findings on effects of the MARK3 gene and how it affects microtubule dynamics in cells, which in turn affect trafficking of RNA and other cargo. He outlined more questions the research aims to answer next.

Click here to view more coverage of the 2024 MDA Conference.

REFERENCES

1. Arnold F. Characterization of Alternative Polyadenylation Events in ALS Highlights New Disease Mechanisms and Novel Gene Therapy Targets. Presented at: 2024 MDA Clinical and Scientific Conference; March 3-6; Orlando, FL.
2. Amyotrophic Lateral Sclerosis (ALS): Causes/Inheritance. MDA website. https://www.mda.org/disease/amyotrophic-lateral-sclerosis/causes-inheritance#:~:text=About%205%2D10%25%20of%20ALS,specific%20region%20of%20a%20chromosome.