Alternative Splicing ; Computational Biology ; Humans ; Organ Specificity

Flowering is a critical transitional stage during plant growth and development, and is closely related to seed production and crop yield. The flowering transition is regulated by complex genetic networks, whereas many flowering-related genes generate multiple transcripts through alternative splicing to regulate flowering time. This paper summarizes the molecular mechanisms of alternative splicing in regulating plant flowering from several perspectives, future research directions are also envisioned.
Alternative Splicing/genetics* ; Arabidopsis/metabolism* ; Arabidopsis Proteins/genetics* ; Flowers/genetics*

Dilated cardiomyopathy (DCM) is a significant contributor to heart failure and can lead to life-threatening cardiovascular events at any stage. RNA-binding motif protein 20 (RBM20) gene mutation is known to be one of the causes of DCM. This mutation exhibits familial aggregation and is associated with arrhythmias, increasing the risk of sudden and early death. This article delves into the characteristics of the RBM20 gene, highlighting its role in regulating alternative splicing of the TTN gene and calcium/calmodulin-dependent protein kinase type II gene. Furthermore, the article provides a summary of treatment options available for DCM caused by RBM20 gene mutations, aiming to enhance clinicians' understanding of the RBM20 gene and provide new ideas for precision medicine treatment.
Humans ; Alternative Splicing ; Cardiomyopathy, Dilated/metabolism* ; Heart Failure/metabolism* ; Mutation

Alternative splicing (AS) is an evolutionarily conserved mechanism that removes introns and ligates exons to generate mature messenger RNAs (mRNAs), extremely improving the richness of transcriptome and proteome. Both mammal hosts and pathogens require AS to maintain their life activities, and inherent physiological heterogeneity between mammals and pathogens makes them adopt different ways to perform AS. Mammals and fungi conduct a two-step transesterification reaction by spliceosomes to splice each individual mRNA (named cis -splicing). Parasites also use spliceosomes to splice, but this splicing can occur among different mRNAs (named trans -splicing). Bacteria and viruses directly hijack the host's splicing machinery to accomplish this process. Infection-related changes are reflected in the spliceosome behaviors and the characteristics of various splicing regulators (abundance, modification, distribution, movement speed, and conformation), which further radiate to alterations in the global splicing profiles. Genes with splicing changes are enriched in immune-, growth-, or metabolism-related pathways, highlighting approaches through which hosts crosstalk with pathogens. Based on these infection-specific regulators or AS events, several targeted agents have been developed to fight against pathogens. Here, we summarized recent findings in the field of infection-related splicing, including splicing mechanisms of pathogens and hosts, splicing regulation and aberrant AS events, as well as emerging targeted drugs. We aimed to systemically decode host-pathogen interactions from a perspective of splicing. We further discussed the current strategies of drug development, detection methods, analysis algorithms, and database construction, facilitating the annotation of infection-related splicing and the integration of AS with disease phenotype.
Animals ; Alternative Splicing/genetics* ; RNA Splicing ; Spliceosomes/metabolism* ; RNA, Messenger/metabolism* ; Communicable Diseases/genetics* ; Mammals/metabolism*

To analyze the expression of splicing factors in gastric cancer using bioinformatics methods and investigate the effect of aberrantly expressed serine/arginine-rich splicing factor(SRSF10)on the phenotype of gastric cancer cells. The RNA-seq data of gastric cancer and paracancerous tissues were downloaded from The Cancer Genome Atlas(TCGA)cancer database,and bioinformatics analysis was performed to obtain the splicing factors differentially expressed in gastric cancer.The splicing factor SRSF10 was selected to investigate its effect on the development of gastric cancer.RNA interference technology was used to construct SRSF10 knockdown gastric cancer cells.MTS,Transwell,and cell scratches were used to study the effect of SRSF10 knockdown on gastric cancer cell phenotype. A total of 48 splicing factors were identified in gastric cancer by a series of bioinformatics techniques,of which 35 were up-regulated and 13 were down-regulated.The splicing factor SRSF10,which was up-regulated,was selected for further study.It was found that the gastric cancer cells after SRSF10 knockdown proliferated more slowly and had lower migration ability than normal gastric cancer cells. Multiple splicing factors are found in gastric cancer and may play an important role in the development of gastric cancer.The splicing factor SRSF10 may contribute to the pathogenesis of gastric cancer.
Alternative Splicing ; Cell Cycle Proteins ; Computational Biology ; Gene Expression Regulation, Neoplastic ; Humans ; RNA Splicing Factors ; Repressor Proteins ; Serine-Arginine Splicing Factors ; Stomach Neoplasms

HExDB is a database for analyzing exon and splicing pattern information in Homo sapiens. HExDB is useful for specific purposes: 1) to design primers for exon amplification from cDNA and 2) to understand the change of ORFs by alternative splicing. HExDB was constructed by integrating data from AltExtron which is the computationally predicted exon database, Ensemble cDNA annotation, and Affymetrix genome tile published recently. Although it may contain false positive data, HExDB is good starting point due to its sensitivity. At present, there are as many as 2,046,519 exons stored in the HExDB. We found that 16.8% of the exons in the database was constitutive exons and 83.1% were novel gene exons.
Alternative Splicing* ; Animals ; DNA, Complementary ; Ecthyma, Contagious ; Exons* ; Genome ; Humans* ; Open Reading Frames

Alternative splicing of pre-mRNA is an important mechanism for regulating gene function at the post-transcription level and for producing proteomic diversity in higher eukaryotes. The alternative splicing is regulated by the interaction between diverse cis-acting elements and trans-acting factors. Alternative splicing events of oncogenes, tumor suppressor genes and metastasis suppressor genes are associated with the initiation and development of human neoplasms. The protein isoforms sourced from alternative splicing take part in regulating the gene transcription, cell cycle, apoptosis of cells, and playing a role in tumor growth. It is possible for molecular therapy to target directly isoforms of protein produced by alternative splicing or to interfere with the process of alternative splicing.
Alternative Splicing ; genetics ; Humans ; Neoplasms ; genetics ; RNA Precursors ; metabolism ; RNA, Neoplasm ; analysis ; Transcription, Genetic

The serotonergic system in vertebrates and invertebrates has been a focus for over 50 years and will likely continue in the future. Recently, genomic analysis and discovery of alternative splicing and differential expression in tissues have increased the knowledge of serotonin (5-HT) receptor types. Comparative studies can provide useful insights to the wide variety of mechanistic actions of 5-HT responsible for behaviors regulated or modified by 5-HT. To determine cellular responses and influences on neural systems as well as the efferent control of behaviors by the motor units, preparations amenable to detailed studies of synapses are beneficial as working models. The invertebrate neuromuscular junctions (NMJs) offer some unique advantages for such investigations; action of 5-HT at crustacean NMJs has been widely studied, and leech and Aplysia continue to be key organisms. However, there are few studies in insects likely due to the focus in modulation within the CNS and lack of evidence of substantial action of 5-HT at the Drosophila NMJs. There are only a few reports in gastropods and annelids as well as other invertebrates. In this review we highlight some of the key findings of 5-HT actions and receptor types associated at NMJs in a variety of invertebrate preparations in hopes that future studies will build on this knowledge base.
Alternative Splicing ; Aplysia ; Drosophila ; Gastropoda ; Insects ; Invertebrates ; Knowledge Bases ; Neuromuscular Junction ; Serotonin ; Synapses ; Synaptic Transmission ; Vertebrates

BACKGROUND: CD44 is the principal cell surface receptor for hyaluronate and exists as multiple isoforms generated by the alternative splicing of up to 10 variant exons. Although certain isofroms may play a role in tumor progression and metastasis formation, the precise function and expression of the variant isoforms are less clear. Since on normal eccrine glands CD44 standard isoform(CD44s) is expressed only in eccrine coil secretory cells, it can be considered as a possible marker of this type of differentiation. However little is known about the expression of CD44 variant isofroms(CD44v) in eccrine gland tumors. OBJECTIVE: The purpose of this study was to investigate the immunohistochemical expression of different CD44 isoforms(CD44s, CD44v4, CD44v6) in the eccrine gland tumors. METHODS: Formalin-fixed and paraffin-embedded tissues from 2 cases of eccrine hidrocystoma, 5 cases of syringoma, 2 cases of eccrine poroma, 2 cases of syringofibroadenoma, 2 cases of nodular hidradenoma were immunolabelled with monoclonal antibody directed CD44s, CD44v4, and CD44v6. RESULTS: Except for syringofibroadenoma, the most tumors cells with eccrine ductal differentiation showed negative staining for CD44s, and positive staining for CD44v4 and CD44v6. Syringofibroadenoma exhibited positive staining for CD44s and CD44v4, but negative staining for CD44v6. Eccrine poroma showed negative staining for CD44s, positive staining for CD44v4, and variable intensity of staining for CD44v6 in different areas of the tumors. In case of nodular hidradenoma, small tubular lumina and clear cells were positive for CD44s. CONCLUSION: Our results suggest that CD44 isoforms can not be a useful marker for an eccrine gland tumor with specific differentiation, but its characteristic pattern of distribution might reflect the variety of functional roles of CD44 isoforms in tumorigenesis of eccrine gland tumors.
Acrospiroma ; Alternative Splicing ; Carcinogenesis ; Eccrine Glands* ; Exons ; Hidrocystoma ; Negative Staining ; Neoplasm Metastasis ; Poroma ; Protein Isoforms* ; Syringoma

Alternative splicing (AS) is an important mechanism of producing transcriptome diversity and microarray techniques are being used increasingly to monitor the splice variants. There exist three types of microarrays interrogating AS events-junction, exon, and tiling arrays. Junction probes have the advantage of monitoring the splice site directly. Johnson et al., performed a genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays (Science 302:2141-2144, 2003), which monitored splicing at every known exon-exon junctions for more than 10,000 multi-exon human genes in 52 tissues and cell lines. Here, we describe an algorithm to deduce the relative concentration of isoforms from the junction array data. Non-negative Matrix Factorization (NMF) is applied to obtain the transcript structure inferred from the expression data. Then we choose the transcript models consistent with the ECgene model of alternative splicing which is based on mRNA and EST alignment. The probe-transcript matrix is constructed using the NMF-consistent ECgene transcripts, and the isoform abundance is deduced from the non-negative least squares (NNLS) fitting of experimental data. Our method can be easily extended to other types of microarrays with exon or junction probes.
Alternative Splicing ; Cell Line ; Exons* ; Humans ; Least-Squares Analysis ; Protein Isoforms ; RNA Precursors ; RNA, Messenger ; Transcriptome