# Sleep and diurnal alternative polyadenylation sites associated with human APA-linked brain disorders

## TL;DR

This paper explores how sleep and circadian rhythms affect alternative polyadenylation in the brain and links these changes to human brain disorders.

## Contribution

The study identifies APA sites in rat brains related to sleep and circadian rhythms and connects them to human brain disorder susceptibility genes.

## Key findings

- Unique APAs in rat brains are associated with time-of-day and sleep deprivation.
- Sleep-related PASs are linked to human brain disorder susceptibility genes.
- APA changes may influence mRNA function and contribute to neurological diseases.

## Abstract

Disruption of sleep and circadian rhythms are a comorbid feature of many pathologies, and can negatively influence many health conditions, including neurodegenerative disease, metabolic illness, cancer, and various neurological disorders. Genetic association studies linking sleep and circadian disturbances with disease susceptibility have mainly focused on changes in gene expression due to mutations, such as single-nucleotide polymorphisms. The interaction between sleep and/or circadian rhythms with the use of Alternative Polyadenylation (APA) has been largely undescribed, particularly in the context of other disorders. APA is a process that generates various transcript isoforms of the same gene affecting its mRNA translation, stability, localization, and subsequent function. Here we identified unique APAs expressed in rat brain over time-of-day, immediately following sleep deprivation, and the subsequent recovery period. From these data, we performed a secondary analysis of these sleep- or time-of-day associated PASs with recently described APA-linked human brain disorder susceptibility genes.