premRNAU2

PremRNAU2 is a term used in discussions of pre-mRNA processing to describe the engagement of the U2 small nuclear ribonucleoprotein particle with intron sequences during spliceosome assembly. In eukaryotic gene expression, pre-mRNA splicing removes introns and joins exons, and the U2 snRNP is essential for recognizing the branch point sequence near the 3' end of introns. The premRNAU2 stage marks the initial interaction between the pre-mRNA substrate and the U2 snRNP that predisposes the transcript to catalytic splicing.

Mechanistically, the U2 snRNP binds to the branch point adenosine within the intron, aided by auxiliary proteins of the SF3A and SF3B complexes. This binding stabilizes the pre-mRNA in a conformation compatible with catalysis and positions the branch point for the first transesterification reaction. In this context, the 5' splice site is typically still engaged with U1 snRNA, forming the A complex. The U2–pre-mRNA interaction is a prerequisite for recruiting the U4/U6·U5 tri-snRNP and advancing to the B complex, which drives the chemical steps that generate the lariat intermediate.

The efficiency and accuracy of premRNAU2 recognition are influenced by intron sequence, splice site strength, and regulatory factors that modulate U2 binding. Variants or misregulation of U2 snRNP components, such as SF3B1, can lead to splicing defects and have been linked to diseases including certain cancers and myelodysplastic syndromes. Ongoing research uses structural and biochemical approaches to illuminate the conformational transitions of the U2-containing spliceosome and its role in alternative splicing.