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Apr 22

Research Bit:C9orf72 HRE nucleic acid structures shape disease

Research Bits
The Packard Center welcomed Aaron Hauesler from Thomas Jefferson University to a recent investigator's meeting

Meeting Date: April 17, 2020

Presenter: Aaron Hauesler

Talk Title: C9orf72 HRE nucleic acid structures shape disease


What was the question being asked?

The Haeusler lab seeks to understand how DNA and RNA structures that can form as a result of the C9orf72 hexanucleotide repeat expansion (HRE), contribute to gain of function toxicity in disease pathogenesis.

Why is this important for ALS research?

One important aspect of the C9orf72 HRE are the various structures that the repeat DNA and RNA can form within a cell. In order to identify novel therapeutic strategies for C9orf72 ALS, we must first understand the basic biology of how the C9orf72 HRE and these structures impact cellular function.

What was the take-home message?

Both C9orf72 HRE DNA and RNA can form multiple structures. Early data suggests that different RNA structures formed by G4C2 and G2C4 repeats can differentially interact with specific proteins, potentially impairing their normal cellular functions. Moreover, additional proteins can interact with DNA structures formed by the C9orf72 HRE. Together, this would suggest that both DNA and RNA structures can differentially interfere with normal cellular functions.

How do you think the results of this study might impact future approaches to the treatment of ALS?

While additional work is still underway to determine the biological consequences of these pathological interactions mediated by C9orf72 HRE RNA and DNA structures, the work in the Haeusler lab is poised to uncover novel therapeutic targets for inhibiting specific structure mediated pathological events.

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