Dataset Information

HISTONE DEACETYLASE 15 and MOS4-associated complex subunits 3A/3B coregulate intron retention of ABA-responsive genes.

ABSTRACT: Histone deacetylases (HDAs) play an important role in transcriptional regulation of multiple biological processes. In this study, we investigated the function of HDA15 in abscisic acid (ABA) responses. We used immunopurification coupled with mass spectrometry-based proteomics to identify proteins interacting with HDA15 in Arabidopsis (Arabidopsis thaliana). HDA15 interacted with the core subunits of the MOS4-associated complex (MAC), MAC3A and MAC3B, with interaction between HDA15 and MAC3B enhanced by ABA. hda15 and mac3a/mac3b mutants were ABA-insensitive during seed germination and hyposensitive to salinity. RNA sequencing analysis demonstrated that HDA15 and MAC3A/MAC3B co-regulate ABA-responsive intron retention (IR). Furthermore, HDA15 reduced the histone acetylation level of genomic regions near ABA-responsive IR sites and the association of MAC3B with ABA-responsive pre-mRNA was dependent on HDA15. Our results indicate that HDA15 is involved in ABA responses by interacting with MAC3A/MAC3B to mediate splicing of introns.

SUBMITTER: Tu YT

PROVIDER: S-EPMC9434327 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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HISTONE DEACETYLASE 15 and MOS4-associated complex subunits 3A/3B coregulate intron retention of ABA-responsive genes.

Tu Yi-Tsung YT Chen Chia-Yang CY Huang Yi-Sui YS Chang Chung-Han CH Yen Ming-Ren MR Hsieh Jo-Wei Allison JA Chen Pao-Yang PY Wu Keqiang K

Plant physiology 20220801 1

Histone deacetylases (HDAs) play an important role in transcriptional regulation of multiple biological processes. In this study, we investigated the function of HDA15 in abscisic acid (ABA) responses. We used immunopurification coupled with mass spectrometry-based proteomics to identify proteins interacting with HDA15 in Arabidopsis (Arabidopsis thaliana). HDA15 interacted with the core subunits of the MOS4-associated complex (MAC), MAC3A and MAC3B, with interaction between HDA15 and MAC3B enha ...[more]

PMID: 35670741

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Project description:BackgroundIn-depth study of the intron retention levels of transcripts provide insights on the mechanisms regulating pre-mRNA splicing efficiency. Additionally, detailed analysis of retained introns can link these introns to post-transcriptional regulation or identify aberrant splicing events in human diseases.ResultsWe present IntEREst, Intron-Exon Retention Estimator, an R package that supports rigorous analysis of non-annotated intron retention events (in addition to the ones annotated by RefSeq or similar databases), and support intra-sample in addition to inter-sample comparisons. It accepts binary sequence alignment/map (.bam) files as input and determines genome-wide estimates of intron retention or exon-exon junction levels. Moreover, it includes functions for comparing subsets of user-defined introns (e.g. U12-type vs U2-type) and its plotting functions allow visualization of the distribution of the retention levels of the introns. Statistical methods are adapted from the DESeq2, edgeR and DEXSeq R packages to extract the significantly more or less retained introns. Analyses can be performed either sequentially (on single core) or in parallel (on multiple cores). We used IntEREst to investigate the U12- and U2-type intron retention in human and plant RNAseq dataset with defects in the U12-dependent spliceosome due to mutations in the ZRSR2 component of this spliceosome. Additionally, we compared the retained introns discovered by IntEREst with that of other methods and studies.ConclusionIntEREst is an R package for Intron retention and exon-exon junction levels analysis of RNA-seq data. Both the human and plant analyses show that the U12-type introns are retained at higher level compared to the U2-type introns already in the control samples, but the retention is exacerbated in patient or plant samples carrying a mutated ZRSR2 gene. Intron retention events caused by ZRSR2 mutation that we discovered using IntEREst (DESeq2 based function) show considerable overlap with the retained introns discovered by other methods (e.g. IRFinder and edgeR based function of IntEREst). Our results indicate that increase in both the number of biological replicates and the depth of sequencing library promote the discovery of retained introns, but the effect of library size gradually decreases with more than 35 million reads mapped to the introns.

Project description:BackgroundTau is a microtubule-binding protein encoded by the MAPT gene. Tau is essential for several physiological functions and associated with pathological processes, including Alzheimer's disease (AD). Six tau isoforms are typically described in the central nervous system, but current research paints a more diverse landscape and a more nuanced balance between isoforms. Recent work has described tau isoforms generated by intron 11 and intron 12 retention. This work adds to that evidence, proving the existence of MAPT transcripts retaining intron 3. Our aim is to demonstrate the existence of mature MAPT RNA species that retain intron 3 in human brain samples and to study its correlation with Alzheimer's disease across different regions.MethodsInitial evidence of intron-3-retaining MAPT species come from in silico analysis of RNA-seq databases. We further demonstrate the existence of these mature RNA species in a human neuroepithelioma cell line and human brain samples by quantitative PCR. We also use digital droplet PCR to demonstrate the existence of RNA species that retain either intron 3, intron 12 or both introns.FindingsIntron-3-retaining species are even more prominently present that intron-12-retaining ones. We show the presence of MAPT transcripts that retain both introns 3 and 12. These intron-retaining species are diminished in brain samples of patients with Alzheimer's disease with respect to individuals without dementia. Conversely, relative abundance of intron-3- or intron-12-retaining MAPT species with respect to double-retaining species as well as their percentage of expression with respect to total MAPT are increased in patients with Alzheimer's disease, especially in hippocampal samples. Among these TIR-MAPT species, TIR3+12 double truncation allows better classification potential of Alzheimer's disease samples. Moreover, we find a significant increase in intron-3- or intron-12-retaining species and its relative abundance with respect to double-retaining MAPT species in cerebellum in contrast to frontal lateral cortex and hippocampus in individuals with no signs of dementia.InterpretationIntron retention constitutes a potential mechanism to generate Tau isoforms whose mature RNA expression levels correlate with Alzheimer's pathology showing its potential as a biomarker associated to the disease.FundingThis research was funded by the Spanish Ministry of Science, Innovation and Universities: PGC2018-096177-B-I00 (J.A.); Spanish Ministry of Science and Innovation (MCIN): PID2020-113204GB-I00 (F.H.) and PID2021-123859OB-100 from MCIN/AEI/10.13039/501100011033/FEDER, UE (J.A.). It was also supported by CSIC through an intramural grant (201920E104) (J.A.) and the Centre for Networked Biomedical Research on Neurodegenerative Diseases (J.A.). The Centro de Biología Molecular Severo Ochoa (CBMSO) is a Severo Ochoa Center of Excellence (MICIN, award CEX2021-001154-S).

Dataset Information

HISTONE DEACETYLASE 15 and MOS4-associated complex subunits 3A/3B coregulate intron retention of ABA-responsive genes.

Publications

HISTONE DEACETYLASE 15 and MOS4-associated complex subunits 3A/3B coregulate intron retention of ABA-responsive genes.

Similar Datasets

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