U4U6U5

In molecular biology, the U4/U6/U5 tri-snRNP refers to a large ribonucleoprotein particle that combines three small nuclear ribonucleoproteins (snRNPs): U4, U6, and U5. This complex is a core component of the spliceosome, the molecular machine responsible for removing introns from pre-mRNA and joining exons to form mature messenger RNA.

Composition and role: The tri-snRNP comprises the U4, U6, and U5 snRNPs along with a set of associated proteins that stabilize interactions among the snRNPs. In the early steps of spliceosome assembly, U4 and U6 snRNAs base-pair to form a di-snRNP, which then associates with U5 snRNP to yield the complete tri-snRNP. This assembly is a key prerequisite for forming the active spliceosomal complex.

Function and dynamics: The tri-snRNP is recruited to a pre-mRNA substrate to form the B complex, where it anchors the catalytic core of the spliceosome. Activation of the spliceosome involves unwinding the U4/U6 snRNA duplex, release of U4, and rearrangement that facilitates the first transesterification reaction, marking the transition toward the active splicing state.

Biological and clinical significance: The U4/U6/U5 tri-snRNP is highly conserved across eukaryotes and essential for accurate intron excision. Defects in components of the tri-snRNP or its assembly pathway can cause aberrant splicing and have been linked to several diseases, including certain inherited retinal disorders.

History and naming: The term tri-snRNP reflects the association of the three snRNPs. Biochemical analyses in the late 20th century led to the understanding that this complex acts as a central subunit of the mature spliceosome.