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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

Circular RNAs (circRNAs) are brain-abundant RNAs of mostly unknown functions. To seek their roles in Parkinson's disease (PD), we generated an RNA sequencing resource of several brain region tissues from dozens of PD and control donors. In the healthy substantia nigra (SN), circRNAs accumulate in an age-dependent manner, but in the PD SN this correlation is lost and the total number of circRNAs reduced. In contrast, the levels of circRNAs are increased in the other studied brain regions of PD patients. We also found circSLC8A1 to increase in the SN of PD individuals. CircSLC8A1 carries 7 binding sites for miR-128 and is strongly bound to the microRNA effector protein Ago2. Indeed, RNA targets of miR-128 are also increased in PD individuals, suggesting that circSLC8A1 regulates miR-128 function and/or activity. CircSLC8A1 levels also increased in cultured cells exposed to the oxidative stress-inducing agent paraquat but were decreased in cells treated with the neuroprotective antioxidant regulator drug Simvastatin. Together, our work links circSLC8A1 to oxidative stress-related Parkinsonism and suggests further exploration of its molecular function in PD.

Original languageAmerican English
Article numbere11942
JournalEMBO Molecular Medicine
Volume12
Issue number9
DOIs
StatePublished - 7 Sep 2020

Bibliographical note

Publisher Copyright:
© 2020 The Authors. Published under the terms of the CC BY 4.0 license

Keywords

  • AGO2
  • CircRNA
  • CircSLC8A1
  • Parkinson's disease
  • RNA sequencing

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