Splicing motifs are organized within global structural scaffold of a pre-mRNA

The specific recognition of splice signals at or near the exon-intron junctions is not explained by their weak conservation across the mammalian transcriptome. We explored the possibility of the global structural scaffold of a pre-mRNA guiding early spliceosomal components to the splice signal sequences. We find that mutation in any of the splice signal sequences could disrupt the global structure of a pre-mRNA, and consequently impede recruitment of early spliceosomal components to the pre-mRNA even when their cognate splice signals are intact. We also find distribution of pre-mRNA segments potentially interacting with early spliceosomal component U1 snRNP across the intron, spatial proximity of 5′ and 3′ splice sites within pre-mRNA scaffold, and an interplay between the global structural scaffold and splicing regulatory elements in recruiting early spliceosomal components. These results provide a conceptual base to understand the role of pre-mRNA global structural scaffold in regulating the functionalities of splicing motifs.