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Circular RNAs: the Emerging Class of Non-coding RNAs and Their Potential Role in Human Neurodegenerative Diseases

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Abstract

The exciting world of research with RNAs has to its credit some breakthrough findings that led to newer insights on multiple problems including that of human diseases. After the advent of siRNA, microRNA, and lncRNA, exciting novel molecules called circular RNAs (circRNAs) have been recently described. circRNAs are a class of non-coding RNAs, which are produced by scrambling of exons at the time of splicing. They are primarily produced in the brain region and are naturally present inside the cell. The best known ones so far include a particular type of circRNA namely “circular RNA sponge for miR-7” (ciRS-7 and CDR1as) which is the inhibitor of miR-7 microRNA—known to regulate various diseases like, cancer, neurodegenerative diseases, diabetes, and atherosclerosis. Similarly, another circRNA molecule called circmbl modulates the ratio of linear mRNA by competing with linear muscleblind gene through which it is synthesized. Considering the complex association of these molecules with critical microRNAs and gene families, circRNAs might have important roles in the cause and progression of human diseases. In particular, the multi-factorial nature of neurodegenerative diseases does warrant studies employing novel approaches towards identifying underlying root causes of these ailments. The non-coding RNAs, like circRNAs and microRNAs, could well present a common genetic trigger to multiple factors associated with neurodegenerative diseases. A specific fingerprint of a combination of various marker circRNAs could be explored for early diagnostic purpose as well. Herein, we review the possibility of exploring the role of circRNAs in the context of the central nervous system (CNS) and age-associated neurodegenerative diseases.

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Abbreviations

ADAR1:

Adenosine deaminase acting on RNA

AGO:

Argonaute

ALS:

Amyotrophic lateral sclerosis

CDR1as:

Antisense transcript of cerebellar degeneration-related protein 1

AD:

Alzheimer’s disease

CNS:

Central nervous system

CDR1:

Cerebeller degeneration-related protein 1

circRNA:

Circular RNA

CFH:

Complement factor H

exRNAs:

Extracellular RNAs

fmn :

Formin

HDV:

Hepatitis delta virus

HIPK:

Homeodomain-interacting protein kinase

HD:

Huntington’s disease

tricRNAs:

Intronic circRNAs

EIciRNAs:

Intron-exon circRNAs

IRES:

Internal ribosome entry site

lncRNA:

Long non-coding RNA

mRNA:

Mature RNA

miRNA:

MicroRNA

MBL:

Muscleblind

NDs:

Neurodegenerative diseases

ncRNAs:

Non-coding RNAs

PD:

Parkinson’s disease

piRNAs:

Piwi-interacing RNAs

pre-mRNA:

Precursor-mature RNA

RCRs:

Reverse complementary repeats

rRNA:

Ribosomal RNA

siRNA:

Small interfering RNA

snRNAs:

Small nuclear RNAs

snoRNAs:

Small nucleolar RNAs

SRY:

Sex determining region Y

TDP:

TAR DNA-binding protein

tRNA:

Transfer RNA

UTR:

Untranslated region

ZNF:

Zinc finger

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Acknowledgments

We thank the Council of Scientific and Industrial Research for funding our research; vide Network Project BSC0118 (EpiHeD). CSIR-CDRI Communication number is 9357.

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All the authors (KL, S, HR, BT, and NA) contributed to the writing of the manuscript. All authors read and approved the final manuscript.

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  1. Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, 226 031, India

    Lalit Kumar,  Shamsuzzama, Rizwanul Haque, Tanvi Baghel & Aamir Nazir

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Kumar, L., Shamsuzzama, Haque, R. et al. Circular RNAs: the Emerging Class of Non-coding RNAs and Their Potential Role in Human Neurodegenerative Diseases. Mol Neurobiol 54, 7224–7234 (2017). https://doi.org/10.1007/s12035-016-0213-8

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