# Spliceosome Proteins: Composition, Function, and Regulation

## Introduction to Spliceosome Proteins

### What is the Spliceosome?

The spliceosome is a large, dynamic ribonucleoprotein (RNP) complex that catalyzes the removal of introns from precursor messenger RNA (pre-mRNA) in a process called splicing. This essential step in eukaryotic gene expression requires the precise recognition of exon-intron boundaries, the cleavage at the 5′ splice site, and the ligation of adjacent exons. The spliceosome is composed of five small nuclear ribonucleoprotein particles (snRNPs)—U1, U2, U4/U6, and U5—along with numerous non-snRNP protein factors. Together, these components assemble anew on each intron in a highly ordered, ATP-dependent manner. For a detailed structural overview, see [Spliceosome Structure](/knowledge/molecular-biology/spliceosome-structure).

The spliceosome is often described as one of the most complex macromolecular machines in the cell, rivaling the ribosome in its intricacy. However, unlike the ribosome, which is a stable entity, the spliceosome is assembled *de novo* for each splicing event and disassembles after catalysis. This dynamic nature is reflected in its protein composition, which changes dramatically as the complex progresses through assembly, activation, and catalysis.

### Why Spliceosome Proteins Matter

Spliceosome proteins are not merely structural scaffolds; they are the functional drivers of splicing. They perform the critical tasks of recognizing splice sites, positioning the catalytic core, and remodeling RNA-RNA and RNA-protein interactions. Without these proteins, the pre-mRNA would not be correctly processed, leading to the production of aberrant proteins or the degradation of faulty transcripts via nonsense-mediated decay.

The importance of spliceosome proteins is underscored by their evolutionary conservation. Many core splicing factors in yeast (*Saccharomyces cerevisiae*) have clear orthologs in humans, and the fundamental mechanisms of splicing are conserved from yeast to mammals. Moreover, mutations in genes encoding spliceosome proteins cause a range of human diseases, including spinal muscular atrophy, retinitis pigmentosa, and various cancers. Understanding the composition and function of these proteins is therefore not only a matter of basic molecular biology but also has direct translational relevance.

## Core Components: snRNPs and Their Proteins

### The snRNP Complexes

Each snRNP consists of a small nuclear RNA (snRNA) molecule complexed with a set of proteins. The five major snRNPs involved in splicing are U1, U2, U4, U5, and U6. These snRNPs are named after the snRNA they contain: U1 snRNA, U2 snRNA, and so forth. The snRNAs are uridine-rich, non-coding RNAs that range in length from approximately 100 to 200 nucleotides in humans.

The snRNPs can be divided into two classes based on their protein composition. The U1, U2, U4, and U5 snRNPs each contain a common set of seven Sm proteins (B/B′, D1, D2, D3, E, F, and G) that assemble into a ring structure around a conserved sequence motif called the Sm site. The U6 snRNP, in contrast, contains a related set of seven LSm (Sm-like) proteins (LSm2–LSm8) that bind to a distinct sequence element. These core Sm/LSm proteins are essential for the stability of the snRNPs and for their nuclear import.

### Sm and LSm Core Proteins

The Sm proteins are small (approximately 9–25 kDa) proteins that share a conserved Sm domain, a fold consisting of an N-terminal helix and a five-stranded β-sheet. Seven Sm proteins assemble into a doughnut-shaped heptameric ring that binds to the Sm site of the snRNA. This ring structure is critical for snRNP biogenesis: it protects the snRNA from degradation, promotes hypermethylation of the 5′ cap, and facilitates nuclear import.

The LSm proteins are structurally similar to Sm proteins but assemble into a distinct heptameric ring on U6 snRNA. The LSm ring binds to the 3′ end of U6 snRNA and is required for U6 stability and for the formation of the U4/U6 di-snRNP. The LSm proteins also play roles beyond splicing, functioning in mRNA degradation and other RNA processing pathways.

### snRNP-Specific Proteins

In addition to the common Sm/LSm core, each snRNP contains specific proteins that confer unique functions. The U1 snRNP contains three U1-specific proteins: U1-70K, U1A, and U1C. These proteins are involved in the recognition of the 5′ splice site, with U1-70K and U1C stabilizing the base-pairing interaction between U1 snRNA and the pre-mRNA.

The U2 snRNP contains the proteins U2A′, U2B″, and the SF3a and SF3b complexes. The SF3a complex consists of three subunits (SF3a120, SF3a66, SF3a60 in humans), while SF3b has at least seven subunits (SF3b155, SF3b145, SF3b130, SF3b49, SF3b14a, SF3b10, and SF3b14b). These proteins are essential for the stable association of U2 snRNP with the branch point sequence during [spliceosome assembly](/knowledge/molecular-biology/spliceosome-assembly).

The U4/U6/U5 tri-snRNP is the most complex snRNP particle, containing more than 30 proteins. The U5 snRNP carries seven specific proteins: U5-220 (also known as Prp8), U5-116 (Prp28), U5-102 (Prp6), U5-40 (Prp40), U5-15 (Dib1), U5-13, and U5-8. Prp8 is particularly notable as one of the largest and most highly conserved proteins in the spliceosome, playing a central role in the catalytic core. The U4/U6 di-snRNP contains proteins such as Prp3, Prp4, Prp31, and CypH, which are involved in the assembly and stability of the tri-snRNP.

## Non-snRNP Splicing Factors

### Early Recognition Factors

Before the spliceosome assembles, several non-snRNP proteins recognize the cis-acting elements of the pre-mRNA. The branch point binding protein SF1 (also known as BBP in yeast) binds to the branch point sequence. The U2 snRNP auxiliary factor (U2AF) heterodimer consists of a large subunit (U2AF65) that binds to the polypyrimidine tract and a small subunit (U2AF35) that recognizes the conserved AG dinucleotide at the 3′ splice site. These early recognition events are essential for defining the intron and committing the pre-mRNA to the splicing pathway.

The interaction between SF1 and U2AF65 is stabilized by additional factors, including the splicing factor SR proteins (discussed below). Together, these proteins form the commitment complex (E complex), which is the earliest specific complex in [spliceosome assembly](/knowledge/molecular-biology/spliceosome-assembly).

### The Prp19 Complex

The Prp19 complex (also called the NTC, for NineTeen Complex) is a large multi-protein assembly that is essential for the activation of the spliceosome. In yeast, the NTC contains Prp19, Cef1, Clf1, Syf1, Syf2, Isy1, Ntc20, and several other proteins. In humans, the orthologous complex is the Prp19/CDCL5 complex, which includes hPrp19, CDC5L, PLRG1, and BCAS2, among others.

The Prp19 complex is recruited to the spliceosome during the transition from the B complex to the activated B* complex. It is required for the destabilization of U4 snRNA and the establishment of the catalytic core. The Prp19 complex also has ubiquitin ligase activity, and it ubiquitinates several spliceosome components, which may regulate their activity or stability.

### Other Accessory Factors

Beyond the core snRNPs and the Prp19 complex, a large number of accessory proteins associate with the spliceosome at various stages. These include the RNA helicases Prp5, Prp28, Brr2, Prp2, Prp16, Prp22, and Prp43, which use the energy of ATP hydrolysis to remodel RNA-RNA and RNA-protein interactions. Other factors include the cap-binding complex (CBC), which binds to the 5′ cap of the pre-mRNA and promotes splicing of the first intron, and the exon junction complex (EJC) components, which are deposited on the mRNA after splicing and influence downstream processes such as export and translation.

## Spliceosome Assembly and Catalytic Cycle

### Assembly Pathway

The assembly of the spliceosome proceeds through a series of distinct complexes, each characterized by a specific set of proteins and RNA interactions. The pathway is as follows:

1. **E complex (commitment complex):** U1 snRNP base-pairs with the 5′ splice site, and SF1 and U2AF bind to the branch point and polypyrimidine tract/3′ splice site, respectively. This complex is ATP-independent.

2. **A complex (pre-spliceosome):** U2 snRNP stably associates with the branch point sequence, displacing SF1. This step requires ATP hydrolysis and the U2 snRNP protein SF3b. The branch point adenosine is now bulged out, poised for the first catalytic step.

3. **B complex (pre-catalytic spliceosome):** The U4/U6/U5 tri-snRNP joins the complex. At this stage, U4 and U6 are still base-paired, and the complex is not yet catalytically active.

4. **B* complex (activated spliceosome):** The Prp19 complex and the helicase Prp2 promote the dissociation of U4 from U6, allowing U6 to base-pair with U2 snRNA. This rearrangement creates the catalytic core. U1 and U4 snRNPs are released.

5. **C complex (catalytic spliceosome):** The first transesterification reaction occurs, cleaving the 5′ splice site and forming the lariat intermediate. The C complex then rearranges to position the 3′ splice site for the second catalytic step.

6. **Post-catalytic complex and disassembly:** After the second transesterification, the mRNA is released, and the intron lariat is degraded. The snRNPs are recycled for subsequent rounds of splicing.

For a more detailed walkthrough of this pathway, see [Spliceosome Assembly](/knowledge/molecular-biology/spliceosome-assembly).

### ATP-Dependent Remodeling

The assembly and activation of the spliceosome require the action of DExD/H-box RNA helicases. These enzymes use the energy of ATP hydrolysis to unwind RNA duplexes, displace proteins from RNA, and induce conformational changes. Key helicases and their roles include:

- **Prp5:** Remodels the U2 snRNP to promote branch point recognition.
- **Prp28:** Displaces U1 snRNP from the 5′ splice site, allowing U6 to take over.
- **Brr2:** Unwinds the U4/U6 duplex, a critical step in spliceosome activation.
- **Prp2:** Remodels the B* complex, promoting the first catalytic step.
- **Prp16:** Proofreads the first step and promotes the second step.
- **Prp22:** Remodels the C complex to release the mature mRNA.
- **Prp43:** Disassembles the post-catalytic complex and recycles snRNPs.

Each of these helicases acts at a specific point in the cycle, and their activities are tightly regulated to ensure the fidelity of splicing.

### Catalytic Steps

Splicing occurs via two sequential transesterification reactions. In the first step, the 2′-hydroxyl of the branch point adenosine attacks the phosphate at the 5′ splice site, cleaving the pre-mRNA and forming a lariat intermediate. In the second step, the 3′-hydroxyl of the 5′ exon attacks the phosphate at the 3′ splice site, ligating the exons and releasing the intron lariat.

The catalytic core of the spliceosome is formed by U6 snRNA, which coordinates two magnesium ions in a mechanism analogous to that of group II introns. This has led to the classification of the [spliceosome as a ribozyme](/knowledge/molecular-biology/spliceosome-a-ribozyme), with the snRNA providing the catalytic activity and the proteins providing structural support and regulation. For a deeper discussion, see [Spliceosome a Ribozyme](/knowledge/molecular-biology/spliceosome-a-ribozyme).

## Regulatory Proteins: SR and hnRNP Proteins

### SR Proteins as Enhancers

Serine/arginine-rich (SR) proteins are a family of splicing factors characterized by one or two N-terminal RNA recognition motifs (RRMs) and a C-terminal arginine/serine (RS) domain rich in serine and arginine dipeptides. In humans, there are at least 12 classical SR proteins, including SRSF1 (ASF/SF2), SRSF2 (SC35), and SRSF3 (SRp20).

SR proteins bind to exonic splicing enhancers (ESEs) and promote spliceosome assembly by recruiting U1 snRNP to the 5′ splice site and U2AF to the 3′ splice site. They do this through protein-protein interactions: the RS domain of SR proteins interacts with the RS domain of U1-70K and with U2AF35. SR proteins also play roles in other aspects of mRNA metabolism, including export, translation, and nonsense-mediated decay.

The activity of SR proteins is regulated by phosphorylation. SR protein kinases (SRPKs) and the Clk/Sty kinases phosphorylate the RS domain, which controls the subcellular localization of SR proteins and their interactions with other splicing factors. Dephosphorylation by phosphatases such as PP1 and PP2A is also required for splicing, indicating that a cycle of phosphorylation and dephosphorylation is essential for SR protein function.

### hnRNPs as Silencers

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a large family of [RNA-binding proteins](/knowledge/molecular-biology/rna-binding-protein) that associate with pre-mRNA. Unlike SR proteins, hnRNPs generally act as negative regulators of splicing, binding to exonic splicing silencers (ESSs) or intronic splicing silencers (ISSs) and repressing spliceosome assembly.

The hnRNP A/B family (hnRNP A1, A2/B1) is among the best-studied silencers. hnRNP A1 binds to ESS elements and can antagonize the activity of SR proteins by competing for binding sites or by promoting the use of distal splice sites. hnRNP I (also known as polypyrimidine tract binding protein, PTB) binds to the polypyrimidine tract and inhibits U2AF binding, thereby repressing splicing.

The balance between SR proteins and hnRNPs determines the outcome of [alternative splicing](/blog/guides/alternative-splicing) decisions. The relative concentrations of these factors vary between cell types and in response to developmental or environmental signals, providing a mechanism for tissue-specific and condition-specific splicing regulation.

### Exonic and Intronic Splicing Enhancers/Silencers

The cis-acting elements that regulate alternative splicing are classified by their location and function:

| Element | Location | Function | Typical Binding Proteins |
|---------|----------|----------|--------------------------|
| Exonic splicing enhancer (ESE) | Exon | Promotes exon inclusion | SR proteins (SRSF1, SRSF2) |
| Exonic splicing silencer (ESS) | Exon | Promotes exon skipping | hnRNPs (hnRNP A1, hnRNP I) |
| Intronic splicing enhancer (ISE) | Intron | Promotes exon inclusion | SR proteins, tissue-specific factors |
| Intronic splicing silencer (ISS) | Intron | Promotes exon skipping | hnRNPs, PTB |

These elements often function in a context-dependent manner, and a single exon may contain multiple [enhancers and silencers](/knowledge/molecular-biology/enhancer-and-silencer) that integrate signals from various regulatory proteins.

## Methods to Study Spliceosome Proteins

### Genetic and Biochemical Approaches

The study of spliceosome proteins has a rich history rooted in genetics. In the 1980s and 1990s, yeast genetic screens identified many of the core splicing factors. The *prp* (pre-mRNA processing) mutants in *S. cerevisiae* were isolated as temperature-sensitive mutants that accumulated pre-mRNA at the restrictive temperature. Cloning of the corresponding genes revealed the Prp proteins, many of which are conserved in humans.

Biochemical approaches have been equally important. The spliceosome can be assembled *in vitro* using nuclear extracts and radiolabeled pre-mRNA substrates. Native gel electrophoresis and glycerol gradient sedimentation allow the separation of the different spliceosomal complexes (E, A, B, C). Affinity purification using tagged components, such as a tandem affinity purification (TAP) tag on a known splicing factor, enables the isolation of the entire spliceosome for analysis.

Mass spectrometry has revolutionized the field by allowing the comprehensive identification of spliceosome components. Quantitative mass spectrometry can also reveal the dynamics of protein association and dissociation during the splicing cycle. For example, the use of stable isotope labeling by amino acids in cell culture (SILAC) combined with affinity purification has been used to define the protein composition of each spliceosomal complex.

### Structural Biology: Cryo-EM

The determination of high-resolution structures of the spliceosome has been a major achievement of the last decade. Single-particle cryo-electron microscopy (cryo-EM) has been used to solve the structures of the *S. cerevisiae* and human spliceosome at various stages of the splicing cycle. These structures have revealed the molecular architecture of the catalytic core, the arrangement of the snRNAs, and the positions of the protein components.

Cryo-EM structures have been particularly informative for understanding the role of Prp8, which sits at the heart of the catalytic core and contacts both the 5′ splice site and the branch point. The structures have also shown how the Prp19 complex stabilizes the activated spliceosome and how the helicases are positioned to remodel the complex. For an overview of the structural organization, see [Spliceosome Complex](/knowledge/molecular-biology/spliceosome-complex).

### High-Throughput Sequencing

RNA sequencing (RNA-seq) has become an indispensable tool for studying splicing on a genome-wide scale. By comparing the splicing patterns of wild-type and mutant cells, or of cells depleted of specific splicing factors, researchers can identify the targets of individual spliceosome proteins. Cross-linking and immunoprecipitation (CLIP) and its variants (e.g., eCLIP, iCLIP) allow the identification of the RNA binding sites of specific splicing factors across the transcriptome.

These high-throughput approaches have revealed that splicing regulation is far more complex than previously appreciated. Many splicing factors bind to thousands of transcripts, and their effects are often context-dependent, influenced by the local sequence environment, the presence of other factors, and the cellular state.

## Spliceosome Proteins in Disease

### Examples of Splicing Diseases

Mutations in genes encoding spliceosome proteins cause a variety of human diseases. One of the best-characterized examples is spinal muscular atrophy (SMA), a neurodegenerative disorder caused by mutations in the *SMN1* gene. The SMN protein is required for the assembly of Sm core proteins onto snRNAs; its loss leads to reduced levels of snRNPs and widespread splicing defects, particularly in motor neurons.

Another example is retinitis pigmentosa (RP), a form of progressive blindness. Mutations in the genes *PRPF31*, *PRPF3*, *PRPF8*, *PRPF6*, and *SNRNP200* (which encodes the Brr2 helicase) cause autosomal dominant RP. These genes encode proteins of the U4/U6/U5 tri-snRNP, and the mutations are thought to cause haploinsufficiency or dominant-negative effects that impair splicing in retinal cells.

Mutations in the U2 snRNP component SF3B1 are among the most common mutations in myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia (CLL). These mutations alter the branch point recognition specificity of U2 snRNP, leading to widespread changes in alternative splicing.

### Cancer and Splicing Mutations

Spliceosome protein mutations are particularly prevalent in hematological malignancies. Recurrent mutations in *SF3B1*, *SRSF2*, *U2AF1*, and *ZRSR2* are found in a large fraction of MDS, acute myeloid leukemia (AML), and CLL cases. These mutations are often mutually exclusive, suggesting that they converge on common pathways of splicing dysregulation.

The mutant splicing factors typically cause aberrant splicing of specific target genes, including genes involved in DNA damage response, apoptosis, and RNA metabolism. For example, mutant U2AF1 causes altered 3′ splice site selection in hundreds of genes, and mutant SRSF2 affects the splicing of genes with specific sequence motifs.

The dependence of cancer cells on mutant splicing factors has led to the development of therapeutic strategies targeting the spliceosome. The compound pladienolide B and its derivatives (such as H3B-8800) bind to SF3B1 and inhibit spliceosome assembly. These drugs show selective toxicity against cells bearing spliceosome mutations, providing a potential therapeutic window.

## Common Pitfalls and Study Tips

### Misconceptions

Students often encounter several misconceptions when learning about spliceosome proteins:

1. **Confusing snRNPs with the entire spliceosome.** The snRNPs are components of the spliceosome, but the spliceosome also includes many non-snRNP proteins. The spliceosome is not a single stable particle but a dynamic assembly that changes composition throughout the splicing cycle.

2. **Thinking splicing is constitutive.** While some introns are spliced constitutively, the majority of human genes undergo alternative splicing. The regulation of splice site choice by SR proteins and hnRNPs is a critical layer of gene regulation.

3. **Believing the spliceosome is purely protein-based.** The catalytic activity resides in the snRNA components, particularly U6 snRNA. The spliceosome is a ribozyme, and the proteins serve structural and regulatory roles.

4. **Assuming all splicing factors are essential in all contexts.** Many splicing factors are required for the splicing of only a subset of introns. Depletion of a single factor often causes subtle changes in splicing rather than a complete block.

5. **Overlooking the role of ATP.** Spliceosome assembly and remodeling are ATP-dependent processes. The helicases that drive these rearrangements are essential for splicing.

### Study Strategies

To master the material on spliceosome proteins, consider the following strategies:

- **Learn the assembly pathway as a narrative.** Understand why each complex forms and what must happen to transition to the next stage. Focus on the key RNA-RNA interactions and the proteins that promote them.

- **Use tables to organize the snRNP components.** Create a table listing each snRNP, its snRNA, the Sm/LSm proteins, and the specific proteins. This will help you memorize the components and their functions.

- **Connect structure to function.** When learning about a protein like Prp8, think about what its position in the catalytic core means for its function. The cryo-EM structures are helpful for visualizing these relationships.

- **Practice with alternative splicing examples.** Work through specific examples of how SR proteins and hnRNPs regulate exon inclusion or skipping. Understanding the logic of enhancers and silencers is more important than memorizing individual cases.

- **Relate disease mutations to protein function.** For each disease mentioned, ask what the mutated protein normally does and how the mutation might disrupt that function. This will reinforce your understanding of the basic biology.

## Frequently Asked Questions

### Is spliceosome a protein?

No, the spliceosome is not a single protein. It is a large ribonucleoprotein complex composed of both RNA (snRNAs) and proteins. The spliceosome contains five snRNPs (U1, U2, U4/U6, U5) and numerous non-snRNP proteins. The catalytic activity of the spliceosome is provided by the snRNA components, making it a ribozyme, while the proteins play structural, regulatory, and remodeling roles. For a basic definition, see [Spliceosome Definition](/knowledge/molecular-biology/spliceosome-definition).

### What are spliceosome proteins?

Spliceosome proteins are the protein components of the spliceosome. They include the Sm and LSm core proteins that bind to snRNAs, the snRNP-specific proteins (such as U1-70K, U2A′, and Prp8), and the non-snRNP factors (such as SF1, U2AF, and the Prp19 complex). These proteins are involved in recognizing splice sites, assembling the spliceosome, remodeling RNA-RNA interactions, and regulating splicing.

### How many proteins are in the spliceosome?

The number of proteins in the spliceosome varies depending on the stage of the splicing cycle. The human spliceosome is estimated to contain over 150 distinct proteins at its most complex stage (the B complex). However, not all of these proteins are present at every stage; the composition changes dynamically as the spliceosome assembles, catalyzes splicing, and disassembles. The core snRNP proteins are present throughout, while many accessory factors associate only transiently.

### What is the function of spliceosome proteins?

Spliceosome proteins perform several essential functions: they recognize cis-acting elements on the pre-mRNA (such as the 5′ splice site, branch point, and polypyrimidine tract), they position the snRNAs to form the catalytic core, they remodel RNA-RNA and RNA-protein interactions using ATP hydrolysis, and they regulate the fidelity and efficiency of splicing. Some proteins also link splicing to other steps of gene expression, such as mRNA export and translation.

### Are spliceosome proteins enzymes?

Some spliceosome proteins are enzymes, while others are not. The RNA helicases (such as Prp2, Prp16, Prp22, and Brr2) are ATP-dependent enzymes that remodel the spliceosome. The Prp19 complex has ubiquitin ligase activity. However, many spliceosome proteins are structural or scaffolding factors that do not catalyze chemical reactions. Importantly, the catalytic activity of splicing itself is provided by the snRNA components, not by proteins.

### What are SR proteins?

SR proteins are a family of serine/arginine-rich splicing factors that contain one or two RNA recognition motifs and a C-terminal RS domain rich in arginine-serine dipeptides. They bind to exonic splicing enhancers and promote spliceosome assembly by recruiting U1 snRNP and U2AF to the splice sites. SR proteins are regulated by phosphorylation and play key roles in both constitutive and alternative splicing.

### How are spliceosome proteins studied?

Spliceosome proteins are studied using a combination of genetic, biochemical, structural, and computational approaches. Yeast genetics identified many core splicing factors through temperature-sensitive mutants. Biochemical purification and mass spectrometry define the protein composition of spliceosomal complexes. Cryo-electron microscopy provides high-resolution structures. RNA-seq and CLIP identify the targets and binding sites of splicing factors on a genome-wide scale.

## Key Takeaways

- The spliceosome is a dynamic ribonucleoprotein complex composed of five snRNPs (U1, U2, U4/U6, U5) and numerous non-snRNP proteins that assemble anew on each intron.
- The snRNPs contain Sm or LSm core proteins that stabilize the snRNA, along with snRNP-specific proteins that mediate splice site recognition and spliceosome assembly.
- Spliceosome assembly proceeds through defined complexes (E, A, B, B*, C) and requires ATP-dependent remodeling by DExD/H-box RNA helicases.
- The catalytic core of the spliceosome is formed by U6 snRNA, making the [spliceosome a ribozyme](/knowledge/molecular-biology/spliceosome-a-ribozyme); proteins provide structural support and regulation.
- SR proteins and hnRNPs antagonistically regulate alternative splicing by binding to enhancers and silencers, respectively.
- Mutations in spliceosome proteins cause diseases such as spinal muscular atrophy, retinitis pigmentosa, and cancers, and the spliceosome is a target for cancer therapy.
- Modern methods including cryo-EM, mass spectrometry, and RNA-seq have revealed the molecular architecture and regulatory logic of the spliceosome.

## Further Reading

- Santos BPO et al. *Exploring Disordered Regions of Human Spliceosome Proteins*. The journal of physical chemistry letters. 2026. [PubMed 41689531](https://doi.org/10.1021/acs.jpclett.6c00082)
- Zhang M et al. *Use of potassium ion channel and spliceosome proteins as diagnostic biomarkers for sudden unexplained death in schizophrenia*. Forensic science international. 2022. [PubMed 36162298](https://doi.org/10.1016/j.forsciint.2022.111471)
- M. Hetzer et al. *An Atp-Dependent, Ran-Independent Mechanism for Nuclear Import of the U1a and U2b′′ Spliceosome Proteins*. Journal of Cell Biology. 2000. [PubMed 10648562](https://doi.org/10.1083/jcb.148.2.293)
- E. Buoso et al. *Role of spliceosome proteins in the regulation of glucocorticoid receptor isoforms by cortisol and dehydroepiandrosterone*. [Pharmacological Research](/blog/guides/pharmacological-research). 2017. [PubMed 28373129](https://doi.org/10.1016/j.phrs.2017.03.019)
- J. Toretsky et al. *Abstract A39: Alternative splicing in Ewing sarcoma may be driven by phase separation of spliceosome proteins*. 2016. [DOI 10.1158/1538-7445.PEDCA15-A39](https://doi.org/10.1158/1538-7445.PEDCA15-A39)
- Claire A. Schreiber et al. *41. U2 snRNP Spliceosome Proteins Block Recombinant AAV Vector Transduction*. 2015. [DOI 10.1016/S1525-0016(16)33646-2](https://doi.org/10.1016/S1525-0016(16)33646-2)

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