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RNA-binding protein ELAVL4/HuD ameliorates Alzheimer's disease-related molecular changes in human iPSC-derived neurons

ABSTRACT: We generated ELAVL4 knockout (KO), overexpression (OE), and rescue human induced pluripotent stem cell-derived neurons to study the effect that ELAVL4 has on AD-related cellular phenotypes. To gain insight into the molecular cascades involved in neuronal ELAVL4 signaling, we then performed gene expression profiling analysis using data obtained from RNA-seq using triplicate samples for each condition

ORGANISM(S): Homo sapiens

PROVIDER: GSE202985 | GEO | 2022/07/26

REPOSITORIES: GEO

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MicroRNA-sequencing from the striatum of ELAVL4 (HuD) KO mice and wild type littermate adult mice

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2021-09-29 | GSE179652 | GEO

RNA Sequencing analyses of control and HuD KO (Elavl4 null) mouse cortical transcriptomes

Project description:Purpose: The goal of this study was to analyse RNA-seq data to determine the effect of deletion of the RNA-binding protein HuD in transcriptiome-wide alternative splicing and polyadenylation in the neocortex of adult HuD KO vs. wild type littermates (controls) Methods: Cortical mRNA profiles of adult HuD KO (Elavl4 -/-) mice and Control mice were generated by RNA sequencing, in triplicate, using Illumina NovaSeq 6000 platform. The quality of raw RNA-sequencing reads was evaluated using FastQC software (version 0.11.5) and adapters were removed using the Cutadapt (version 1.15) and Trimmomatic (version 0.38) software. Alternative splicing was evaluated using rMATS software (version 4.0.2) and BAM files were converted to BedGraph before examining alternative polyadenylation using DaPars software (version 0.9.1) Methods (cont.): RNA-seq data was aligned to the M musculus genome (UCSC browser, mm10) using STAR (version 2.7.3a), and MultiQC (version 1.8) was used to perform a final quality check on STAR alignment files. If alignments were found to be the same read length and have >80% reads mapped to a unique location, the data was considered good quality and alternative splicing and polyadenylation analyses were performed. Sequence reads per sample were aligned to the mouse genome (build mm10). Results: HuD KO affected alternative splicing of 310 genes, including 17 validated HuD targets such as Cbx3, Cspp1, Snap25 and Gria2. In addition, deletion of HuD affected polyadenylation of 53 genes, with the majority of significantly altered mRNAs shifting towards usage of the proximal polyadenylation signal (PAS), resulting in shorter 3’ untranslated regions (3’ UTRs). Conclusions: HuD KO had a greater effect on alternative splicing than polyadenylation, with many of the affected genes implicated in several neuronal functions and neuropsychiatric disorders.

2021-03-17 | GSE169023 | GEO

Transcriptome-wide analysis of HuD (ELAVL4) RNA interactome and post-transcriptional regulation in a motor neuron cell line

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2018-07-13 | GSE115490 | GEO

Expression data from P0 forebrain of wild-type and Elavl3/Elavl4 double knockout mice.

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