# A role for circular RNAs in schizophrenia

> **NIH NIH R21** · MCLEAN HOSPITAL · 2020 · $164,000

## Abstract

Transcriptional alterations of protein-coding and non-coding RNAs may be a common
intermediate phenotype of both, genetic and environmental contribution to schizophrenia (SZ). Evidence from
studies on micro RNAs and long non-coding RNAs suggest a profound influence of non-coding RNAs
(ncRNAs) on brain function in health and disease. Beyond that, the function of the non-coding transcriptome
remains for the most part unknown. Circular RNAs (circRNAs) are abundant non-coding RNAs that may have a
regulatory role in transcription, translation and other cellular functions. Given their enrichment in the brain, their
dynamic expression across development and in response to neuronal activation, it is conceivable that
circRNAs may have a functional role in SZ. However, little is known about expression and function of circRNAs
in normal human brain tissue and their relevance and function in SZ. Supported by preliminary data, our
central hypotheses are that circRNAs show a region-, sex- and disease-specific expression profile in the brain
and that circRNAs play a causal role in transcriptomic and proteomic changes in SZ. We will test these two
hypotheses through two specific aims: Specific Aim 1 will expand our robust preliminary dataset on
circLARP1B probing its region- and sex-specific expression profile. This aim will also test the hypothesis that
circLARP1B is an upstream regulatory element of the RNA-binding protein LARP1B, which presumably
controls SZ-specific molecular pathways through an interaction with distinct linear target mRNAs. Thus, we will
expand our preliminary findings and investigate the molecular function of circLARP1B, a circRNA that shows a
robust dysregulation in SZ. Specific Aim 2 will assess circRNA and linear RNA expression in the dorsolateral
prefrontal cortex and anterior cingulate cortex in an extended sample of subjects with SZ and the Common
Mind RNAseq database with ~1000 samples. Here, we will test the hypothesis that additional circRNAs from
loci previously implicated in SZ are differentially expressed in regions known to play a key role in SZ. We will
provide evidence for a functional role of circRNAs in pathways implicated in the pathophysiology of SZ. Thus,
we will expand our preliminary findings and investigate the region- and sex-specific expression and function of
circRNAs in pathways altered in SZ. The significance and potential impact of this proposal lays in the fact that
knowledge on the expression and function of circRNAs in the healthy and diseased human brain is sparse. By
generating data on region- and sex-specific circRNA expression and molecular function of circRNAs
reproducibly dysregulated in SZ, we obtain preliminary data supporting an in-depth study of the molecular
function of circRNAs in interaction with known genetic, epigenetic, transcriptional and proteomic alterations in
SZ as part of a future R01 proposal. This will provide novel insights into the contribution of the non-coding
transcriptome to the...

## Key facts

- **NIH application ID:** 9828106
- **Project number:** 5R21MH117609-02
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** Sabina Berretta
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $164,000
- **Award type:** 5
- **Project period:** 2018-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828106

## Citation

> US National Institutes of Health, RePORTER application 9828106, A role for circular RNAs in schizophrenia (5R21MH117609-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9828106. Licensed CC0.

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