Paper of the month

Soreq's Lab: A Parkinson's disease CircRNAs Resource reveals a link between circSLC8A1 and oxidative stress

Mor Hanan, Alon Simchovitz, Nadav Yayon, Shani Vaknine, Roni Cohen‐Fultheim, Miriam Karmon, Nimrod Madrer, Talia Miriam, Rohrlich Moria Maman, Estelle R Bennett, David S Greenberg, Eran Meshorer, Erez Y Levanon, Hermona Soreq, Sebastian Kadener

EMBO Mol Med (2020)e11942 (2020)

Lay summary:

Circular RNAs are the products of an unusual circularization process of RNA transcripts and are known to accumulate in the ageing brain, but their role in neurodegenerative diseases is incompletely understood. In our study, we sought circular RNAs in three brain regions of patients with Parkinson’s disease and matched controls from the Netherlands brain Bank. Profiling total RNAs in the disease-affected substantial Nigra, the stress-responding amygdala and the medial temporal gyrus found age-related accumulation of circular RNAs in the latter two regions, but not in the diseased substantial Nigra where most of the neurons have been lost. However, one circular RNA product of a Ca++ regulating gene, named SLC8A1 accumulated in the Parkinsonian substantial Nigra; and it also accumulated in cultured neurons exposed to the neurotoxic agent paraquat, in a manner suppressible by neuroprotective cholesterol-reducing statins. Our paper offers a Resource of all of the circular RNAs in the studied brain regions and argues that the circular SLC8A1 transcript operates to regain control over Ca++ ions in the sick substantial Nigra via ‘sponging’ microRNAs attracted to it.

“Working memory”