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The Plant Journal : For Cell and... Aug 2020Soybean nodulation is a highly controlled process that involves complex gene regulation at both transcriptional and post-transcriptional levels. In the present study, we...
Soybean nodulation is a highly controlled process that involves complex gene regulation at both transcriptional and post-transcriptional levels. In the present study, we profiled gene expression changes, alternative splicing events, and DNA methylation patterns during nodule formation, development, and senescence. The transcriptome data uncovered key transcription patterns of nodule development that included 9669 core genes and 7302 stage-specific genes. Alternative splicing analysis uncovered a total of 2323 genes that undergo alternative splicing events in at least one nodule developmental stage, with activation of exon skipping and repression of intron retention being the most common splicing events in nodules compared to roots. Approximately 40% of the differentially spliced genes were also differentially expressed at the same nodule developmental stage, implying a substantial association between gene expression and alternative splicing. Genome-wide-DNA methylation analysis revealed dynamic changes in nodule methylomes that were specific to each nodule stage, occurred in a sequence-specific manner, and impacted the expression of 1864 genes. An attractive hypothesis raised by our data is that increased DNA methylation may contribute to the efficiency of alternative splicing. Together, our results provide intriguing insights into the associations between gene expression, alternative splicing, and DNA methylation that may shape transcriptome complexity and proteome specificity in developing soybean nodules.
Topics: Alternative Splicing; DNA Methylation; Gene Expression Profiling; Gene Expression Regulation, Plant; Genes, Plant; Plant Root Nodulation; Root Nodules, Plant; Glycine max
PubMed: 32491251
DOI: 10.1111/tpj.14861 -
British Journal of Cancer May 2022Alternative splicing (AS) is a key process in which precursor RNAs produce different mature RNAs, and the disorder of AS is a key factor in promoting cancer development.... (Review)
Review
Alternative splicing (AS) is a key process in which precursor RNAs produce different mature RNAs, and the disorder of AS is a key factor in promoting cancer development. Compared with coding RNA, studies on the functions of long non-coding RNAs (lncRNAs) are far from enough. In fact, lncRNA is an important participant and regulator in the process of AS. On the one hand, lncRNAs regulate cancer progression as AS products of precursor messenger RNA (mRNA), but on the other hand, precursor lncRNA generates cancer-related abnormal splicing variants through AS. In addition, lncRNAs directly or indirectly regulate the AS events of downstream target genes, thus affecting the occurrence and development of cancer. Here, we reviewed how lncRNAs regulate AS and influence oncogenesis in different ways.
Topics: Alternative Splicing; Cell Transformation, Neoplastic; Humans; Neoplasms; RNA, Long Noncoding; RNA, Messenger
PubMed: 34750493
DOI: 10.1038/s41416-021-01600-w -
The Journal of Neuroscience : the... Apr 2023Alternative splicing of AMPA-type glutamate receptors (AMPARs) and allosteric modulation by auxiliary subunits, such as transmembrane AMPAR regulatory proteins (TARPs),...
Alternative splicing of AMPA-type glutamate receptors (AMPARs) and allosteric modulation by auxiliary subunits, such as transmembrane AMPAR regulatory proteins (TARPs), are two important mechanisms that regulate the time course of glutamatergic neurotransmission. Prior work has shown that alternative splicing of the flip/flop cassette profoundly regulates TARP γ2 modulation, where flip receptor gating exhibits robust sensitivity to TARPs while flop isoforms are relatively insensitive to TARP modulation. Whether this splice variant-specific regulation extends to other auxiliary subunit families, such as cornichons (CNIHs), GSG1L, or CKAMPs, remains unknown. Here, we demonstrate that CNIH-3 modulation is unaffected by AMPAR alternative splicing due to inherent differences in how CNIH-3 and TARP γ2 modify channel gating. CNIH-3 slows receptor deactivation from the outset of current decay, consistent with structural evidence showing its point of contact at the level of the pore. In contrast, TARP γ2 acts via the KGK site of the ligand-binding domain (LBD) to slow the onset of desensitization. Although GSG1L and CKAMP44 primarily slow recovery from desensitization, their effects on channel gating are unaffected by alternative splicing, further underlining that structural events leading to the onset and recovery from desensitization are separable. Together, this work establishes that alternative splicing and TARP auxiliary subunits form a unique partnership that governs fast glutamatergic signaling at central synapses. Since proteomic studies suggest that all native AMPARs co-assemble with at least two TARPs, allosteric coupling between the flip/flop cassette and TARPs may represent a common design element in all AMPAR complexes of the mammalian brain. All fast excitatory neurotransmission in the mammalian brain is mediated by AMPA-type glutamate receptors (AMPARs). The time course of AMPAR gating can be regulated by two distinct mechanisms: alternative splicing of the flip/flop cassette and association with auxiliary subunits. Although these regulatory mechanisms have been well studied individually, it is not clear whether alternative splicing impacts auxiliary protein modulation of AMPARs. Here, we compare the four main families of AMPAR auxiliary subunits, transmembrane AMPAR regulatory proteins (TARPs; γ2), cornichons (CNIH-3), GSG1L and CKAMPs (CKAMP44), and find a privileged relationship between TARPs and the flip/flop cassette that is not shared by others. The flop cassette acts as a master switch to override TARP action, and this coupling represents a way to fine-tune AMPAR signaling.
Topics: Animals; Receptors, AMPA; Alternative Splicing; Proteomics; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Glutamic Acid; Mammals
PubMed: 36931708
DOI: 10.1523/JNEUROSCI.2293-22.2023 -
Philosophical Transactions of the Royal... Jun 2018It is widely known that epigenetic modifications are important in regulating transcription, but several have also been reported in alternative splicing. The regulation... (Review)
Review
It is widely known that epigenetic modifications are important in regulating transcription, but several have also been reported in alternative splicing. The regulation of pre-mRNA splicing is important to explain proteomic diversity and the misregulation of splicing has been implicated in many diseases. Here, we give a brief overview of the role of epigenetics in alternative splicing and disease. We then discuss the bioinformatics methods that can be used to model interactions between epigenetic marks and regulators of splicing. These models can be used to identify alternative splicing and epigenetic changes across different phenotypes.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.
Topics: Alternative Splicing; Computational Biology; Epigenesis, Genetic; Humans; Proteome
PubMed: 29685977
DOI: 10.1098/rstb.2017.0073 -
International Journal of Molecular... Feb 2018Alternative mRNA splicing is an important mechanism in expansion of proteome diversity by production of multiple protein isoforms. However, emerging evidence indicates... (Review)
Review
Alternative mRNA splicing is an important mechanism in expansion of proteome diversity by production of multiple protein isoforms. However, emerging evidence indicates that only a limited number of annotated protein isoforms by alternative splicing are detected, and the coding sequence of alternative splice variants usually is only slightly different from that of the canonical sequence. Nevertheless, mis-splicing is associated with a large array of human diseases. Previous reviews mainly focused on hereditary and somatic mutations in cis-acting RNA sequence elements and trans-acting splicing factors. The importance of environmental perturbations contributed to mis-splicing is not assessed. As significant changes in exon skipping and splicing factors expression levels are observed with diet-induced obesity, this review focuses on several well-known alternatively spliced metabolic factors and discusses recent advances in the regulation of the expressions of splice variants under the pathophysiological conditions of obesity. The potential of targeting the alternative mRNA mis-splicing for obesity-associated diseases therapies will also be discussed.
Topics: Alternative Splicing; Animals; Humans; Models, Biological; Molecular Targeted Therapy; Obesity; RNA, Messenger
PubMed: 29473878
DOI: 10.3390/ijms19020632 -
Molecules (Basel, Switzerland) Aug 2023Cancer is a global health concern with rising incidence, morbidity, and mortality. The interaction between the tumor and immune cells within the tumor microenvironment... (Review)
Review
Cancer is a global health concern with rising incidence, morbidity, and mortality. The interaction between the tumor and immune cells within the tumor microenvironment is facilitated by signaling pathways driven by immunomodulatory proteins. Alternative splicing regulates the production of multiple immunomodulatory proteins with diverse functionality from a single mRNA transcript. Splicing factors are pivotal in modulating alternative splicing processes but are also subject to regulation. The dysregulation of alternative splicing may result from splicing factor (SF) abnormal expression levels and mutations in the cis and trans-acting elements and small nuclear RNA (snRNA) molecules. Aberrant splicing may generate abnormal mRNA transcripts encoding isoforms with altered functions that contribute to tumorigenesis or cancer progression. This review uncovers the complexity of immunomodulatory genes splicing dysregulation in oncogenesis. Identifying specific immunomodulatory splicing isoforms that contribute to cancer could be utilized to improve current immunotherapeutic drugs or develop novel therapeutic interventions for cancer.
Topics: Humans; Carcinogenesis; Cell Transformation, Neoplastic; Genetic Engineering; Alternative Splicing; RNA, Messenger; Tumor Microenvironment
PubMed: 37630236
DOI: 10.3390/molecules28165984 -
Journal of the American Society of... Oct 2020
Topics: Alternative Splicing; Animals; Gene Expression; Kidney; Mice; Protein Isoforms; RNA Isoforms; RNA, Messenger; Sequence Analysis, RNA
PubMed: 32883701
DOI: 10.1681/ASN.2020081180 -
International Journal of Molecular... Apr 2023The post-transcriptional regulation of gene expression, in particular alternative splicing (AS) events, substantially contributes to the complexity of eukaryotic...
The post-transcriptional regulation of gene expression, in particular alternative splicing (AS) events, substantially contributes to the complexity of eukaryotic transcriptomes and proteomes [...].
Topics: Alternative Splicing; Genomics; Biological Evolution; Transcriptome; Stress, Physiological
PubMed: 37047681
DOI: 10.3390/ijms24076708 -
Trends in Cancer Apr 2021Most human genes undergo alternative splicing (AS), and dysregulation of alternative splicing contributes to tumor initiation and progression. Computational analysis of... (Review)
Review
Most human genes undergo alternative splicing (AS), and dysregulation of alternative splicing contributes to tumor initiation and progression. Computational analysis of genomic and transcriptomic data enables the systematic characterization of alternative splicing and its functional role in cancer. In this review, we summarize the latest computational approaches to studying alternative splicing in cancer and the current limitations of the most popular tools in this field. Finally, we describe some of the current computational challenges in the characterization of the role of alternative splicing in cancer.
Topics: Alternative Splicing; Animals; Computational Biology; Humans; Neoplasms; RNA, Messenger
PubMed: 33500226
DOI: 10.1016/j.trecan.2020.12.015 -
Biological Research Mar 2023Drought stress has significantly hampered agricultural productivity worldwide and can also result in modifications to DNA methylation levels. However, the dynamics of...
BACKGROUND
Drought stress has significantly hampered agricultural productivity worldwide and can also result in modifications to DNA methylation levels. However, the dynamics of DNA methylation and its association with the changes in gene transcription and alternative splicing (AS) under drought stress are unknown in linseed, which is frequently cultivated in arid and semiarid regions.
RESULTS
We analysed AS events and DNA methylation patterns in drought-tolerant (Z141) and drought-sensitive (NY-17) linseed under drought stress (DS) and repeated drought stress (RD) treatments. We found that the number of intron-retention (IR) and alternative 3' splice site (Alt3'SS) events were significantly higher in Z141 and NY-17 under drought stress. We found that the linseed response to the DS treatment was mainly regulated by transcription, while the response to the RD treatment was coregulated by transcription and AS. Whole genome-wide DNA methylation analysis revealed that drought stress caused an increase in the overall methylation level of linseed. Although we did not observe any correlation between differentially methylated genes (DMGs) and differentially spliced genes (DSGs) in this study, we found that the DSGs whose gene body region was hypermethylated in Z141 and hypomethylated in NY-17 were enriched in abiotic stress response Gene Ontology (GO) terms. This finding implies that gene body methylation plays an important role in AS regulation in some specific genes.
CONCLUSION
Our study is the first comprehensive genome-wide analysis of the relationship between linseed methylation changes and AS under drought and repeated drought stress. Our study revealed different interaction patterns between differentially expressed genes (DEGs) and DSGs under DS and RD treatments and differences between methylation and AS regulation in drought-tolerant and drought-sensitive linseed varieties. The findings will probably be of interest in the future. Our results provide interesting insights into the association between gene expression, AS, and DNA methylation in linseed under drought stress. Differences in these associations may account for the differences in linseed drought tolerance.
Topics: DNA Methylation; Flax; Droughts; Alternative Splicing; Stress, Physiological; Gene Expression Profiling; Gene Expression Regulation, Plant; Transcriptome
PubMed: 36922868
DOI: 10.1186/s40659-023-00424-7