# Whole-Genome and Poly(A)+Transcriptome Analysis of the Drosophila Mutant agnts3 with Cognitive Dysfunctions

## TL;DR

This study explores genetic and transcriptomic differences in a Drosophila mutant with cognitive issues, identifying genes that may contribute to its behavior under stress.

## Contribution

The study identifies novel genes (MED23, Spn42De, prosalpha1) potentially linked to cognitive dysfunction in a Drosophila mutant.

## Key findings

- High-effect agnts3-specific mutations include MED23 and Spn42De, associated with intellectual disorders.
- Transcriptomic differences between strains involve stress response genes, long non-coding RNAs, and transposons.
- Expression of prosalpha1 and Spn42De in agnts3 changes under stress, but limk1 shows no interstrain differences.

## Abstract

The temperature-sensitive Drosophila mutant agnts3 exhibits the restoration of learning defects both after heat shock (HS) and under hypomagnetic conditions (HMC). Previously, agnts3 was shown to have an increased level of LIM kinase 1 (LIMK1). However, its limk1 sequence did not significantly differ from that of the wild-type strain Canton-S (CS). Here, we performed whole-genome and poly(A)-enriched transcriptome sequencing of CS and agnts3 males normally, after HMC, and after HS. Several high-effect agnts3-specific mutations were identified, including MED23 (regulation of HS-dependent transcription) and Spn42De, the human orthologs of which are associated with intellectual disorders. Pronounced interstrain differences between the transcription profiles were revealed. Mainly, they included the genes of defense and stress response, long non-coding RNAs, and transposons. After HS, the differences between the transcriptomes became less pronounced. In agnts3, prosalpha1 was the only gene whose expression changed after both HS and HMC. The normal downregulation of prosalpha1 and Spn42De in agnts3 was confirmed by RT-PCR. Analysis of limk1 expression did not reveal any interstrain differences or changes after stress. Thus, behavioral differences between CS and agnts3 both under normal and stressed conditions are not due to differences in limk1 transcription. Instead, MED23, Spn42De, and prosalpha1 are more likely to contribute to the agnts3 phenotype.