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International Journal of Molecular... Sep 2023Transcription and alternative splicing (AS) are now appreciated in plants, but few studies have examined the effects of changing ploidy on transcription and AS. In this...
Transcription and alternative splicing (AS) are now appreciated in plants, but few studies have examined the effects of changing ploidy on transcription and AS. In this study, we showed that artificially autododecaploid plants of London plane ( × (Aiton) Willd) had few flowers relative to their hexaploid progenitors. Transcriptome analysis based on full-length Oxford Nanopore Technologies (ONTs) and next-generation sequencing (NGS) revealed that the increased ploidy level in × led to more transcribed isoforms, accompanied by an increase in the number of isoforms per gene. The functional enrichment of genes indicated that novel genes transcribed specifically in the dodecaploids may have been highly correlated with the ability to maintain genome stability. The dodecaploids showed a higher number of genes with upregulated differentially expressed genes (DEGs) compared with the hexaploid counterpart. The genome duplication of × resulted mainly in the DEGs involved in basic biological pathways. It was noted that there was a greater abundance of alternative splicing (AS) events and AS genes in the dodecaploids compared with the hexaploids in × . In addition, a significant difference between the structure and expression of AS events between the hexaploids and dodecaploids of was found. Of note, some DEGs and differentially spliced genes (DSGs) related to floral transition and flower development were consistent with the few flower traits in the dodecaploids of × . Collectively, our findings explored the difference in transcription and AS regulation between the hexaploids and dodecaploids of × and gained new insight into the molecular mechanisms underlying the few-flower phenotype of × . These results contribute to uncovering the regulatory role of transcription and AS in polyploids and breeding few-flower germplasms.
Topics: Alternative Splicing; Magnoliopsida; London; Plant Breeding; Flowers; Protein Isoforms; Gene Expression Regulation, Plant; Transcriptome
PubMed: 37833935
DOI: 10.3390/ijms241914486 -
Cells Dec 2023Alternative splicing changes are closely linked to aging, though it remains unclear if they are drivers or effects. As organisms age, splicing patterns change, varying... (Review)
Review
Alternative splicing changes are closely linked to aging, though it remains unclear if they are drivers or effects. As organisms age, splicing patterns change, varying gene isoform levels and functions. These changes may contribute to aging alterations rather than just reflect declining RNA quality control. Three main splicing types-intron retention, cassette exons, and cryptic exons-play key roles in age-related complexity. These events modify protein domains and increase nonsense-mediated decay, shifting protein isoform levels and functions. This may potentially drive aging or serve as a biomarker. Fluctuations in splicing factor expression also occur with aging. Somatic mutations in splicing genes can also promote aging and age-related disease. The interplay between splicing and aging has major implications for aging biology, though differentiating correlation and causation remains challenging. Declaring a splicing factor or event as a driver requires comprehensive evaluation of the associated molecular and physiological changes. A greater understanding of how RNA splicing machinery and downstream targets are impacted by aging is essential to conclusively establish the role of splicing in driving aging, representing a promising area with key implications for understanding aging, developing novel therapeutical options, and ultimately leading to an increase in the healthy human lifespan.
Topics: Humans; Alternative Splicing; RNA, Messenger; Protein Isoforms; RNA Splicing Factors; Aging; Nonsense Mediated mRNA Decay
PubMed: 38132139
DOI: 10.3390/cells12242819 -
Chinese Medical Journal Jan 2020Alternative splicing can generate various structural and functional protein isoforms. Recently, accumulating evidence shows a relationship between alternative splicing... (Review)
Review
OBJECTIVE
Alternative splicing can generate various structural and functional protein isoforms. Recently, accumulating evidence shows a relationship between alternative splicing and cancer. Cancer is a complex and chronic disease that involves malignant transformation. In this review, we consider alternative splicing events in relation to the hallmarks of cancer cells, and discuss current therapies to treat cancer-related to alternative splicing.
DATA SOURCES
Data cited in this article are from the PubMed and Embase database, primarily focusing on research published from 2000 to 2018.
STUDY SELECTION
Articles were selected with the search terms "alternative splicing," "cancer cell," "tumor microenvironment," and "therapy."
RESULTS
Alternative splicing plays an important role in tumorigenesis, development, and escape from cell death. Taking this trait of cancer cells into consideration will allow more definite diagnoses of cancer, and allow the development of more effective medicines to intervene in cancer that could focus on controlling alternative splicing or competitively binding to the final products.
CONCLUSIONS
Alternative splicing is common in cancer cells. Consideration of alternative splicing may allow different strategies for cancer therapy or the identification of novel biomarkers for cancer diagnosis.
Topics: Alternative Splicing; Animals; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Protein Isoforms
PubMed: 31764175
DOI: 10.1097/CM9.0000000000000542 -
International Journal of Molecular... Jul 2017Pre-mRNA splicing is the process by which introns are removed and the protein coding elements assembled into mature mRNAs. Alternative pre-mRNA splicing provides an... (Review)
Review
Pre-mRNA splicing is the process by which introns are removed and the protein coding elements assembled into mature mRNAs. Alternative pre-mRNA splicing provides an important source of transcriptome and proteome complexity through selectively joining different coding elements to form mRNAs, which encode proteins with similar or distinct functions. In mammals, previous studies have shown the role of alternative splicing in regulating the function of the immune system, especially in the regulation of T-cell activation and function. As lower vertebrates, teleost fish mainly rely on a large family of pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs) from various invading pathogens. In this review, we summarize recent advances in our understanding of alternative splicing of piscine PRRs including peptidoglycan recognition proteins (PGRPs), nucleotide binding and oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) and their downstream signaling molecules, compared to splicing in mammals. We also discuss what is known and unknown about the function of splicing isoforms in the innate immune responses against pathogens infection in mammals and teleost fish. Finally, we highlight the consequences of alternative splicing in the innate immune system and give our view of important directions for future studies.
Topics: Alternative Splicing; Animals; Carrier Proteins; Fishes; Immunity; Mammals; RNA Precursors
PubMed: 28714877
DOI: 10.3390/ijms18071530 -
Trends in Biochemical Sciences Feb 2017Alternative splicing is commonly believed to be a major source of cellular protein diversity. However, although many thousands of alternatively spliced transcripts are... (Review)
Review
Alternative splicing is commonly believed to be a major source of cellular protein diversity. However, although many thousands of alternatively spliced transcripts are routinely detected in RNA-seq studies, reliable large-scale mass spectrometry-based proteomics analyses identify only a small fraction of annotated alternative isoforms. The clearest finding from proteomics experiments is that most human genes have a single main protein isoform, while those alternative isoforms that are identified tend to be the most biologically plausible: those with the most cross-species conservation and those that do not compromise functional domains. Indeed, most alternative exons do not seem to be under selective pressure, suggesting that a large majority of predicted alternative transcripts may not even be translated into proteins.
Topics: Alternative Splicing; Exons; Protein Isoforms; Proteome; Proteomics
PubMed: 27712956
DOI: 10.1016/j.tibs.2016.08.008 -
Cell Proliferation Feb 2024Alternative splicing (AS) disruption has been linked to disorders of muscle development, as well as muscular atrophy. However, the precise changes in AS patterns that...
Alternative splicing (AS) disruption has been linked to disorders of muscle development, as well as muscular atrophy. However, the precise changes in AS patterns that occur during myogenesis are not well understood. Here, we employed isoform long-reads RNA-seq (Iso-seq) and single-cell RNA-seq (scRNA-seq) to investigate the AS landscape during myogenesis. Our Iso-seq data identified 61,146 full-length isoforms representing 11,682 expressed genes, of which over 52% were novel. We identified 38,022 AS events, with most of these events altering coding sequences and exhibiting stage-specific splicing patterns. We identified AS dynamics in different types of muscle cells through scRNA-seq analysis, revealing genes essential for the contractile muscle system and cytoskeleton that undergo differential splicing across cell types. Gene-splicing analysis demonstrated that AS acts as a regulator, independent of changes in overall gene expression. Two isoforms of splicing factor TRA2B play distinct roles in myogenic differentiation by triggering AS of TGFBR2 to regulate canonical TGF-β signalling cascades differently. Our study provides a valuable transcriptome resource for myogenesis and reveals the complexity of AS and its regulation during myogenesis.
Topics: Alternative Splicing; Protein Isoforms; RNA Splicing; Transcriptome; Muscle Development; Gene Expression Profiling
PubMed: 37705195
DOI: 10.1111/cpr.13545 -
Genes Jun 2019In recent years, the knowledge generated by decoding the human genome has allowed groundbreaking genetic research to better understand genomic architecture and...
In recent years, the knowledge generated by decoding the human genome has allowed groundbreaking genetic research to better understand genomic architecture and heritability in healthy and disease states. The vast amount of data generated over time and yet to be generated provides the basis for translational research towards the development of preventive and therapeutic strategies for many conditions. In this special issue, we highlight the discoveries of disease-associated and protective DNA variations in common human diseases and developmental disorders.
Topics: Alternative Splicing; DNA; Genetic Variation; Genome, Human; Genome-Wide Association Study; Genomics; Humans; Precision Medicine
PubMed: 31200548
DOI: 10.3390/genes10060450 -
Nature Reviews. Molecular Cell Biology Nov 2009Alternative splicing of mRNA precursors provides an important means of genetic control and is a crucial step in the expression of most genes. Alternative splicing... (Review)
Review
Alternative splicing of mRNA precursors provides an important means of genetic control and is a crucial step in the expression of most genes. Alternative splicing markedly affects human development, and its misregulation underlies many human diseases. Although the mechanisms of alternative splicing have been studied extensively, until the past few years we had not begun to realize fully the diversity and complexity of alternative splicing regulation by an intricate protein-RNA network. Great progress has been made by studying individual transcripts and through genome-wide approaches, which together provide a better picture of the mechanistic regulation of alternative pre-mRNA splicing.
Topics: Alternative Splicing; Gene Expression Regulation; Genomics; Humans; RNA Precursors; Signal Transduction
PubMed: 19773805
DOI: 10.1038/nrm2777 -
Developmental Cell Mar 2022Alternative splicing generates distinct mRNA variants and is essential for development, homeostasis, and renewal. Proteins of the serine/arginine (SR)-rich splicing...
Alternative splicing generates distinct mRNA variants and is essential for development, homeostasis, and renewal. Proteins of the serine/arginine (SR)-rich splicing factor family are major splicing regulators that are broadly required for organ development as well as cell and organism viability. However, how these proteins support adult organ function remains largely unknown. Here, we used the continuously growing mouse incisor as a model to dissect the functions of the prototypical SR family protein SRSF1 during tissue homeostasis and renewal. We identified an SRSF1-governed alternative splicing network that is specifically required for dental proliferation and survival of progenitors but dispensable for the viability of differentiated cells. We also observed a similar progenitor-specific role of SRSF1 in the small intestinal epithelium, indicating a conserved function of SRSF1 across adult epithelial tissues. Thus, our findings define a regulatory mechanism by which SRSF1 specifically controls progenitor-specific alternative splicing events to support adult tissue homeostasis and renewal.
Topics: Alternative Splicing; Animals; Epithelium; Homeostasis; Mice; RNA Splicing; Serine-Arginine Splicing Factors
PubMed: 35202586
DOI: 10.1016/j.devcel.2022.01.011 -
Molecular Ecology Oct 2021Understanding the contribution of different molecular processes to evolution and development is crucial for identifying the mechanisms of adaptation. Here, we used...
Understanding the contribution of different molecular processes to evolution and development is crucial for identifying the mechanisms of adaptation. Here, we used RNA-sequencing data to test the importance of alternative splicing and differential gene expression in a case of parallel adaptive evolution, the replicated postglacial divergence of the salmonid fish Arctic charr (Salvelinus alpinus) into sympatric benthic and pelagic ecotypes across multiple independent lakes. We found that genes differentially spliced between ecotypes were mostly not differentially expressed (<6% overlap) and were involved in different biological processes. Differentially spliced genes were primarily enriched for muscle development and functioning, while differentially expressed genes were involved in metabolism, immunity and growth. Furthermore, alternative splicing and gene expression were mostly controlled by independent cis-regulatory quantitative trait loci (<3.4% overlap). Cis-regulatory regions were associated with the parallel divergence in splicing (16.5% of intron clusters) and expression (6.7%-10.1% of differentially expressed genes), indicating shared regulatory variation across ecotype pairs. Contrary to theoretical expectation, we found that differentially spliced genes tended to be highly central in regulatory networks ("hub genes") and were annotated to significantly more gene ontology terms compared to nondifferentially spliced genes, consistent with a higher level of pleiotropy. Together, our results suggest that the concerted regulation of alternative splicing and differential gene expression through different regulatory regions leads to the divergence of complementary processes important for local adaptation. This provides novel insights into the importance of contrasting but putatively complementary molecular processes in rapid parallel adaptive evolution.
Topics: Alternative Splicing; Animals; Ecotype; Gene Expression; Salmonidae; Sympatry
PubMed: 33502030
DOI: 10.1111/mec.15817