Spliceosome proteins

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Spliceosome proteins

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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The spliceosome is a large, dynamic ribonucleoprotein (RNP) complex that is found in the nucleus of eukaryotic cells. It is an assembly of small nuclear RNAs (snRNA) and a range of proteins (>150 in humans) that contribute to its function [8]. The spliceosome acts to excise introns from pre-mRNA transcripts and ligate exons to generate mature transcripts. Spliceosome dysfunction is associated with human conditions, including neurodevelopmental disorders (due to genetic defects in the PPIL1, PRP17 and CRNKL1) [5] and craniofacial abnormalities (due to mutations in the SNRPB, SF3B4, and EFTUD2 genes). Pharmacological modulation of spliceosome proteins is considered as a therapeutic strategy for the treatment of certain cancers [2,4]. RNA binding motif protein 39 (RBM39) is an example of a spliceosome protein with specific pharmaceutical agents in pre-clinical and clinical development [3,6-7].

Targets

RNA binding motif protein 39 Show summary »« Hide summary

Target Id

3329

Nomenclature

RNA binding motif protein 39

Previous and unofficial names

RNA binding motif protein 3 | coactivator of activating protein-1 and estrogen receptors (CAPER) | RNA-binding region (RNP1, RRM) containing 2 (RNPC2)

Genes

RBM39 (Hs), Rbm39 (Mm), Rbm39 (Rn)

Ensembl ID

ENSG00000131051 (Hs), ENSMUSG00000027620 (Mm), ENSRNOG00000019848 (Rn)

UniProtKB AC

Q14498 (Hs), Q8VH51 (Mm)

Ligands

indisulam (Binding) (molecular glue degrader)

tasisulam (Binding) (molecular glue degrader)

E7820 (Binding) (molecular glue degrader) [1]

Comment

The RBM39 protein is a spliceosome component that has roles in steroid hormone receptor-mediated transcription and alternative splicing. It is a target of pharmaceutical interest based on its ability to modulate the alternative splicing of genes involved in cancer occurrence and progression. The aryl sulfonamides indisulam and tasisulam have been identified as molecular glue class degraders of RBM39. Next-generation RBM39 molecular glue degraders are in development pipelines, including REC-1245 (Recursion; phase 1/2 for advanced solid tumours), and ST-00937 and ST-01156 (Seed Therapeutics; for Ewing sarcoma and other solid tumours) - structures not disclosed as of September 2025.

References

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1. Faust TB, Yoon H, Nowak RP, Donovan KA, Li Z, Cai Q, Eleuteri NA, Zhang T, Gray NS, Fischer ES. (2020) Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15. Nat Chem Biol, 16 (1): 7-14. [PMID:31686031]

2. Hong Z, Mo T, Zhou P, Chen J, Li X. (2025) Progress of estrogen receptor and spliceosome in endometrial carcinoma. Front Endocrinol (Lausanne), 16: 1586191. [PMID:40927288]

3. Kohsaka S, Yagishita S, Shirai Y, Matsuno Y, Ueno T, Kojima S, Ikeuchi H, Ikegami M, Kitada R, Yoshioka KI et al.. (2024) A molecular glue RBM39-degrader induces synthetic lethality in cancer cells with homologous recombination repair deficiency. NPJ Precis Oncol, 8 (1): 117. [PMID:38789724]

4. Mahlab-Aviv S, Swissa KO, Arafat M, Zohar K, Peretz AR, Linial M, Sperling R. (2025) Nuclear Roles of Spliceosome-Associated microRNAs in Neuronal Cancer Cells. Int J Mol Sci, 26 (17). [PMID:40943278]

5. Ray Das S, Sullivan R, Ruegg MSG, Horsfield J, Doran J, Poke G, de Vries N, Duerinckx S, Lederer D, Haniffa M et al.. (2025) Recurrent de novo variants in the spliceosomal factor CRNKL1 are associated with severe microcephaly and pontocerebellar hypoplasia with seizures. Am J Hum Genet, 112 (7): 1722-1732. [PMID:40857589]

6. Singh S, Fang J, Jin H, Van De Velde LA, Cortes A, Chen J, Natarajan S, Poon E, Wu Q, Morton CL et al.. (2025) RBM39 degrader invigorates innate immunity to eradicate neuroblastoma despite cancer cell plasticity. Nat Commun, 16 (1): 8287. [PMID:40962798]

7. Yang Y, Li Z, Yang Y, Xiao P, He Z, Zhang Z, Li Y, Shi L, Wang X, Tao Y et al.. (2025) The RBM39 degrader indisulam inhibits acute megakaryoblastic leukemia by altering the alternative splicing of ZMYND8. Cell Biosci, 15 (1): 46. [PMID:40223119]

8. Zhang X, Zhan X, Yan C, Zhang W, Liu D, Lei J, Shi Y. (2019) Structures of the human spliceosomes before and after release of the ligated exon. Cell Res, 29 (4): 274-285. [PMID:30728453]

How to cite this family page

Database page citation:

Spliceosome proteins. Accessed on 13/12/2025. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1122.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Buneman OP, Faccenda E, Harding SD, Spedding M, Cidlowski JA, Fabbro D, Davenport AP, Striessnig J, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Introduction and Other Protein Targets. Br J Pharmacol. 180 Suppl 2:S1-22.