Pre-messenger RNA spliceosome (Spliceosome)

The pre-messenger RNA (pre-mRNA) spliceosome is a massive, dynamic ribonucleoprotein (RNP) complex responsible for the precise removal of non-coding introns and the ligation of coding exons from precursor messenger RNA (Nature Reviews Molecular Cell Biology, 2017). This process, known as splicing, is essential for the generation of mature mRNA and the diversification of the proteome through alternative splicing (PubMed: 25233399). The spliceosome is composed of five small nuclear ribonucleoproteins (snRNPs)—U1, U2, U4, U5, and U6—along with hundreds of associated proteins that assemble in a stepwise fashion on the pre-mRNA (UniProt). Mutations in core spliceosomal components, particularly SF3B1, U2AF1, and SRSF2, are frequently observed in hematologic malignancies like myelodysplastic syndromes (MDS) and certain solid tumors, leading to aberrant splicing and oncogenesis (NIH, 2021). Therapeutic strategies targeting the spliceosome include small-molecule inhibitors that bind to the SF3B complex to induce cell death in cancer cells and antisense oligonucleotides (ASOs) or small molecules that modulate splicing to treat genetic disorders like spinal muscular atrophy (PubMed: 30104378). Because splicing is a fundamental cellular process, drugs targeting the spliceosome must balance efficacy against the risk of systemic toxicity and off-target effects on global gene expression (PubMed: 29335235).

Other names

SpliceosomeSpliceosomal complexsnRNP complexPre-mRNA spliceosome

Inhibition of the SF3B complex to prevent U2 snRNP recruitment or modulation of specific splice sites to promote exon inclusion or skipping (PubMed: 29335235, PubMed: 30104378).