5DonorSpleißstelle

5DonorSpleißstelle, also known as the 5' donor splice site, is the boundary at the 5' end of an intron in eukaryotic pre-mRNA where splicing begins to remove the intron. It lies at the exon–intron junction, immediately downstream of the preceding exon. In most introns, the donor site starts with the dinucleotide GT in the DNA (GU in RNA) at the +1 and +2 positions of the intron, consistent with the GT–AG rule that governs many splice junctions. The donor site is part of a degenerate consensus around the boundary, commonly described as AG|GURAGU, where the GUR region and surrounding bases influence splice-site strength and recognition.

Recognition and function: During spliceosome assembly, the donor site is recognized primarily by U1 snRNP, which base-pairs with the donor sequence to define the 5' boundary. Additional proteins, including SR proteins and other splicing factors, stabilize this interaction and facilitate recruitment of downstream components. This leads to the proper removal of the intron and ligation of exons via a lariat intermediate and subsequent catalytic steps.

Biological and clinical significance: Accurate 5' donor splice sites are essential for correct gene expression. Mutations at the donor site or nearby regulatory elements can disrupt splicing, causing exon skipping, intron retention, or activation of cryptic splice sites. Such aberrations can result in frameshifts or truncated proteins and are associated with various genetic diseases. In some genes, alternative splicing uses different donor sites to generate multiple mRNA isoforms, contributing to protein diversity and tissue-specific regulation.