21 May 2020
New potential treatment for slowing down amyotrophic lateral sclerosis
Published online 7 December 2014
Certain types of RNA may be a target to protect certain neurodegenerative diseases
An international research team has discovered that a special type of RNA fragments (tiRNAs) and their DNA analogues could protect stress-exposed motor neurons.
The scientists claim these RNA fragments assemble into unique, guanine-rich short RNA structures, known as G-quadruplex (G4). These promote formation of stress granules that can protect motor neurons from stress and death.
The researchers, including Mohamed Emara from Qatar Biomedical Research Institute, Qatar, and Cairo University, Egypt, have found that selected G4-assembling tiRNAs bind to a protein called YB-1. This inhibits the synthesis process of certain proteins, leading to formation of the stress granules.
To understand the mechanism by which translation is blocked by tiRNAs and tiDNAs, the researchers performed experiments in a cell-free mammalian system that mimics the steps of protein synthesis. They found that after tiRNAs binds to YB-1, tiDNAs displace the cap-binding complex from messenger RNAs, thus inhibiting translation initiation.
When they delivered tiDNAs into cultured motor neurons, tiDNAs partially rescued motor neurons from the toxic effects of stress.
“This suggests that tiRNAs and their DNA analogues may serve as novel compounds for the development of a new class of drugs to protect stress-exposed motor neurons in amyotrophic lateral sclerosis, a neurodegenerative disease,” says the study’s lead author, Pavel Ivanov from Brigham and Women’s Hospital, USA.
- Ivanov, P. et al. G-quadruplex structures contribute to the neuroprotective effects of angiogenin-induced tRNA fragments. Proc. Natl Acad. Sci. USA http://dx.doi.org/10.1073/pnas.1407361111 (2014).