# Role of circular RNAs in autophagy regulation and neuronal development and function in psychiatric disorders

> **NIH NIH P20** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2021 · $280,520

## Abstract

Although ignored until recently for not complying with the central dogma of molecular biology, 
non-coding RNAs (ncRNAs) are emerging as important novel regulators of diverge cellular 
processes. The capacity of ncRNAs to engage in "molecular multitasking" positions them to link 
multiple genetic risk factors for polygenic human genetic disorders, such as psychiatric diseases, 
into functional networks. Circular RNAs (circ RNAs) are a novel category of non-coding RNAs that 
are derived from the back-splicing and covalent joining of exons and introns of protein-coding 
genes, yet lack the capacity to become translated into protein. Recent studies have suggested 
that circ RNAs are enriched in the brain, are developmentally regulated, and are abundant in 
dendrites and synapses. Despite this, nothing is known about the function of circ RNAs in the 
mammalian brain and their potential involvement in autophagy and neuro psychiatric disease. 
Autophagy is a coordinated lysosomal process for the degradation and recycling of cellular 
components, organelles, and protein aggregates that has been heavily implicated in the 
pathophysiology of neurodegenerative disorders. However, recent data suggest that numerous 
autophagy-associated genes display reduced expression in postmortem brains of subjects with 
psychiatric disorders and that neurons utilize autophagy during normal neuronal development and 
function. Despite the above, the importance of autophagy in psychiatric disease pathogenesis 
and pathophysiology has not been fully elucidated. Our proposed research aims in examining the 
role of altered in psychiatric disorders circ RNAs that are either derived from autophagy-related 
genes or are upstream regulators of autophagy gene expression in neuronal autophagy and 
development and function. I specifically propose the following 3 aims. Aim 1: Test the hypothesis 
that alterations in psychiatric disease-associated circRNAs dysregulate linear gene expression 
related to autophagy and neuronal development and function. Aim 2: Test the hypothesis that 
manipulation of psychiatric disease-related circ RNAs ca n alter autophagy and neuronal 
development and function. Aim 3: Test the hypothesis that treatment with autophagy- inducing 
drugs ca n rescue circ R NA- mediated alterations in neuronal development and function. Take n 
together our proposed research will elucidate the mechanisms that underlie the effects of 
autophagy-associated circ RNAs on neuron a l autophagy and function, while examining in parallel 
the irrelevance for psychiatric disease therapeutics.

## Key facts

- **NIH application ID:** 10249124
- **Project number:** 5P20GM121176-05
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Nikolaos mellios
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $280,520
- **Award type:** 5
- **Project period:** 2017-09-01 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249124

## Citation

> US National Institutes of Health, RePORTER application 10249124, Role of circular RNAs in autophagy regulation and neuronal development and function in psychiatric disorders (5P20GM121176-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10249124. Licensed CC0.

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