Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (706 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature messenger rna produce protein isoforms in which one part of the isoforms is common while the other parts are different.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Alternative Splicings; Splicings, Alternative; Splicing, Alternative; RNA Splicing, Alternative; Alternative RNA Splicing; Alternative RNA Splicings; RNA Splicings, Alternative; Splicing, Alternative RNA.
Where it fits in the MeSH classification
- Broader topics
- RNA Splicing
- See also
- Protein Isoforms; RNA Splice Sites; Nested Genes
Related concepts
- Exons
- Messenger Rna
- Protein Isoforms
Research landscape
PubMed indexes 27,619 records tagged with the MeSH heading “Alternative Splicing” (counts retrieved 2026-10-29). 4,870 of them (17.6%) were published from 2020 onward, and the busiest period so far is 2000-2009 with 9,975 records.
Reviews account for 2,734 records (9.9%) and meta-analyses for 24. Randomized controlled trials number 12 (0.0%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 4,269 |
| 2000-2009 | 9,975 |
| 2010-2019 | 8,505 |
| 2020 onward | 4,870 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 2,734 | 9.9% |
| Meta-analyses | 24 | 0.1% |
| Randomized controlled trials | 12 | 0.0% |
Method: PubMed query "Alternative Splicing"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in molecular biology
Molecular biology establishes mechanisms through controlled experiments, often in simplified systems such as purified proteins, cultured cells or model organisms. Such work can show what is possible in a defined system, but whether a pathway matters in a whole organism or in human disease needs further evidence. Check the experimental system, whether findings were reproduced by independent groups, and whether the authors tested the mechanism directly or inferred it from correlation.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| A spatial long-read approach at near-single-cell resolution reveals developmental regulation of splicing and polyadenylation sites in distinct cortical layers and cell types | 2025 | Research article Design not recorded in structured metadata | 19 | cc by PMID 40883294 · DOI · PMC12397408 |
| Alternative Splicing in Tumorigenesis and Cancer Therapy | 2025 | Review article Design not recorded in structured metadata | 15 | cc by PMID 40563429 · DOI · PMC12190615 |
| NAD+ reverses Alzheimer's neurological deficits via regulating differential alternative RNA splicing of EVA1C | 2025 | Research article Design not recorded in structured metadata | 13 | cc by PMID 41202143 · DOI · PMC12594206 |
| Transcriptional readthrough precedes alternative splicing programs triggered in CML cells by imatinib | 2026 | Research article Design not recorded in structured metadata | 6 | cc by PMID 41860998 · DOI · PMC13004010 |
A spatial long-read approach at near-single-cell resolution reveals developmental regulation of splicing and polyadenylation sites in distinct cortical layers and cell types [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Genome-wide spatial long-read approaches often lack single-cell resolution and yield limited read lengths.
- Closing excerpt
- More generally, our technologies enable exciting observations for any complex tissue.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
Genome-wide spatial long-read approaches often lack single-cell resolution and yield limited read lengths. Here, we introduce spatial ISOform sequencing (Spl-ISO-Seq), which reveals exons and polyadenylation sites with near-single-cell resolution. Spl-ISO-Seq selects long cDNAs and doubles to triples read lengths compared to standard preparations. Adding a highly specific software tool (Spl-ISOquant) and comparing human post-mortem pre-puberty (8-11 years) to post-puberty (16-19 years) visual cortex samples, we find that cortex harbors stronger splicing and poly(A)-site regulation than white matter. However, oligodendrocyte regulation is stronger in white matter. Among cortical layers, layer 4 has the most developmentally-regulated splicing changes in excitatory neurons and in poly(A) sites. We also find repeat elements downstream of developmentally-regulated layer 4 exons. Overall, alternative splicing changes are linked to post-synaptic structure and function. These results root developmental splicing changes during puberty in specific layers and cell types. More generally, our technologies enable exciting observations for any complex tissue.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40883294 · DOI · PMC12397408
Alternative Splicing in Tumorigenesis and Cancer Therapy [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Alternative splicing (AS) is a pivotal post-transcriptional mechanism that expands the functional diversity of the proteome by enabling a single gene to generate multiple mRNA and protein isoforms.
- Closing excerpt
- Finally, we address the challenges and future prospects of targeting AS for personalized cancer therapies, emphasizing its potential in precision medicine.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (243 words)
Alternative splicing (AS) is a pivotal post-transcriptional mechanism that expands the functional diversity of the proteome by enabling a single gene to generate multiple mRNA and protein isoforms. This process, which involves the differential inclusion or exclusion of exons and introns, is tightly regulated by splicing factors (SFs), such as serine/arginine-rich proteins (SRs), heterogeneous nuclear ribonucleoproteins (hnRNPs), and RNA-binding motif (RBM) proteins. These factors recognize specific sequences, including 5' and 3' splice sites and branch points, to ensure precise splicing. While AS is essential for normal cellular function, its dysregulation is increasingly implicated in cancer pathogenesis. Aberrant splicing can lead to the production of oncogenic isoforms that promote tumorigenesis, metastasis, and resistance to therapy. Furthermore, such abnormalities can cause the loss of tumor-suppressing activity, thereby contributing to cancer development. Importantly, abnormal AS events can generate neoantigens, which are presented on tumor cell surfaces via major histocompatibility complex (MHC) molecules, suggesting novel targets for cancer immunotherapy. Additionally, splice-switching oligonucleotides (SSOs) have shown promise as therapeutic agents because they modulate splicing patterns to restore normal gene function or induce tumor-suppressive isoforms. This review explores the mechanisms of AS dysregulation in cancer, its role in tumor progression, and its potential as a therapeutic target. We also discuss innovative technologies, such as high-throughput sequencing and computational approaches, that are revolutionizing the study of AS in cancer. Finally, we address the challenges and future prospects of targeting AS for personalized cancer therapies, emphasizing its potential in precision medicine.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40563429 · DOI · PMC12190615
NAD+ reverses Alzheimer's neurological deficits via regulating differential alternative RNA splicing of EVA1C [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Dysfunctional alternative splicing events (ASEs) in RNA are markers of aging and Alzheimer's disease (AD).
- Closing excerpt
- We propose that NAD+ reduces AD pathologies, at least partially, via amplification of the NAD+-EVA1C splicing axis, pointing to a potential splice-switching therapy for AD.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (158 words)
Dysfunctional alternative splicing events (ASEs) in RNA are markers of aging and Alzheimer's disease (AD). As a key neuronal resilience metabolite, the oxidized nicotinamide adenine dinucleotide (NAD+) slows down AD progression in preclinical studies with several clinical trials ongoing. However, the underlying molecular mechanisms around how NAD+ enhances neuronal resilience, especially whether it has any effect on ASEs, have remained elusive. This study shows that NAD+ augmentation corrects the ASEs of many genes via a key protein, EVA1C (epithelial V-like antigen 1 homolog C), which is involved in neuronal development and activities. EVA1C is reduced in the hippocampus in patients with AD compared to cognitively normal ones. NAD+-induced memory retention is partially dependent on EVA1C, as adeno-associated virus-based Eva1c knockdown in the hippocampal CA1 region annuls NAD+-induced memory improvement in pathological Tau-bearing mice. We propose that NAD+ reduces AD pathologies, at least partially, via amplification of the NAD+-EVA1C splicing axis, pointing to a potential splice-switching therapy for AD.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41202143 · DOI · PMC12594206
Transcriptional readthrough precedes alternative splicing programs triggered in CML cells by imatinib [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Cellular stresses regulate transcriptional readthrough, whereby RNA polymerase II elongates past a gene's polyadenylation cleavage site without RNA cleavage.
- Closing excerpt
- Thus, imatinib can provoke a cascade of early changes to transcription and splicing fidelity that may lead to longer-term adjustments in gene expression, cancer cell differentiation, and the development of therapy resistance.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (155 words)
Cellular stresses regulate transcriptional readthrough, whereby RNA polymerase II elongates past a gene's polyadenylation cleavage site without RNA cleavage. Readthrough has been reported in several cancer types. Here, we use long-read sequencing of nascent RNA to quantify transcriptional readthrough in chronic myeloid leukemia (CML) cells and characterize early responses to the targeted therapeutic, imatinib. We show that the amount, length, and gene specificity of readthrough increase within 1 hour, before gene expression and alternative splicing alterations emerge. Notably, imatinib-dependent messenger RNA (mRNA) isoform changes involved "readthrough chimeras," in which exons from an upstream gene are alternatively spliced to exons in a downstream gene. Altered mRNA isoforms and chimera levels were detected in imatinib-resistant K562 cells as well as cells of patients with CML. Thus, imatinib can provoke a cascade of early changes to transcription and splicing fidelity that may lead to longer-term adjustments in gene expression, cancer cell differentiation, and the development of therapy resistance.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41860998 · DOI · PMC13004010
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article RNA sequencing: the teenage years [5]
- Research article Alternative splicing as a regulator of development and tissue identity [6]
- Research article Alternative Splicing Regulatory Networks: Functions, Mechanisms, and Evolution [7]
- Research article Roles and mechanisms of alternative splicing in cancer - implications for care [8]
- Research article RNA splicing dysregulation and the hallmarks of cancer [9]
- Research article The physiology of alternative splicing [10]
References
- Foord C, Prjibelski AD, Hu W, Michielsen L, Vandelli A, Narykov O, et al.. A spatial long-read approach at near-single-cell resolution reveals developmental regulation of splicing and polyadenylation sites in distinct cortical layers and cell types. . 2025. PMID 40883294 · DOI · PMC12397408
- Chen H, Tang J, Xiang J. Alternative Splicing in Tumorigenesis and Cancer Therapy. . 2025. PMID 40563429 · DOI · PMC12190615
- Ai R, Mao L, Jin X, Campos-Marques C, Zhang SQ, Pan J, et al.. NAD+ reverses Alzheimer's neurological deficits via regulating differential alternative RNA splicing of EVA1C. . 2025. PMID 41202143 · DOI · PMC12594206
- Podszywałow-Bartnicka P, Shine M, Lin J, Neugebauer KM. Transcriptional readthrough precedes alternative splicing programs triggered in CML cells by imatinib. . 2026. PMID 41860998 · DOI · PMC13004010
- Stark R, Grzelak M, Hadfield J. RNA sequencing: the teenage years. Nat Rev Genet. 2019. PMID 31341269 · DOI
- Baralle FE, Giudice J. Alternative splicing as a regulator of development and tissue identity. Nat Rev Mol Cell Biol. 2017. PMID 28488700 · DOI · PMC6839889
- Ule J, Blencowe BJ. Alternative Splicing Regulatory Networks: Functions, Mechanisms, and Evolution. Mol Cell. 2019. PMID 31626751 · DOI
- Bonnal SC, López-Oreja I, Valcárcel J. Roles and mechanisms of alternative splicing in cancer - implications for care. Nat Rev Clin Oncol. 2020. PMID 32303702 · DOI
- Bradley RK, Anczuków O. RNA splicing dysregulation and the hallmarks of cancer. Nat Rev Cancer. 2023. PMID 36627445 · DOI · PMC10132032
- Marasco LE, Kornblihtt AR. The physiology of alternative splicing. Nat Rev Mol Cell Biol. 2023. PMID 36229538 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.