Circular RNA Expression and Interaction Patterns Are Perturbed in Amyotrophic Lateral Sclerosis

Chiara Aquilina-Reid; Samuel Brennan; Ashton Curry-Hyde; Guus M Teunisse; The Nygc Als Consortium; Michael Janitz

doi:10.3390/ijms232314665

Circular RNA Expression and Interaction Patterns Are Perturbed in Amyotrophic Lateral Sclerosis

Int J Mol Sci. 2022 Nov 24;23(23):14665. doi: 10.3390/ijms232314665.

Authors

Chiara Aquilina-Reid¹, Samuel Brennan¹, Ashton Curry-Hyde², Guus M Teunisse¹, The Nygc Als Consortium³, Michael Janitz^{2

4}

Affiliations

¹ GenieUs Genomics Pty Ltd., Sydney, NSW 2010, Australia.
² School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
³ The New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA.
⁴ Paul Flechsig Institute for Brain Research, University of Leipzig, 04103 Leipzig, Germany.

Abstract

Circular RNAs (circRNAs) are a type of long noncoding RNA that are highly abundant and highly conserved throughout evolution and exhibit differential expression patterns in various tissue types in multiple diseases, including amyotrophic lateral sclerosis (ALS). The most well-known function of circRNAs is their ability to act as microRNA (miRNA) sponges. This entails circRNA binding to miRNA, which would otherwise target and degrade messenger RNA, thus affecting gene expression. This study analyzed ALS patient samples from three spinal cord regions to investigate circular transcriptome perturbation and circular RNA-microRNA-mRNA interactions. Using stringent statistical parameters, we identified 92 differentially expressed circRNAs across the spinal cord tissues with the aim of identifying specific circRNAs with biomarker potential. We also found evidence for differential expression of 37 linear RNAs possibly due to miRNA sequestration by circRNAs, thus revealing their potential as novel biomarkers and therapeutic candidates for ALS.

Keywords: amyotrophic lateral sclerosis; circular RNAs; microRNAs; spinal cord; transcriptome sequencing.

MeSH terms

Amyotrophic Lateral Sclerosis* / genetics
Biomarkers
Gene Expression Profiling
Humans
MicroRNAs* / genetics
MicroRNAs* / metabolism
RNA / genetics
RNA / metabolism
RNA, Circular / genetics
RNA, Messenger / genetics
Transcriptome

Substances

RNA, Circular
RNA
MicroRNAs
RNA, Messenger
Biomarkers

Grants and funding

A.C.-H. was supported by Australian Government Research Training Program Scholarship. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.