DNA-Encoded Chromatin Structural Intron Boundary Signals Identify Conserved Genes with Common Function

Abstract

The regulation of metazoan gene expression occurs in part by pre-mRNA splicing into mature RNAs. Signals affecting the efficiency and specificity with which introns are removed have not been completely elucidated. Splicing likely occurs cotranscriptionally, with chromatin structure playing a key regulatory role. We calculated DNA encoded nucleosome occupancy likelihood (NOL) scores at the boundaries between introns and exons across five metazoan species. We found that (i) NOL scores reveal a sequence-based feature at the introns on both sides of the intron-exon boundary; (ii) this feature is not part of any recognizable consensus sequence; (iii) this feature is conserved throughout metazoa; (iv) this feature is enriched in genes sharing similar functions: ATPase activity, ATP binding, helicase activity, and motor activity; (v) genes with these functions exhibit different genomic characteristics; (vi) in vivo nucleosome positioning data confirm ontological enrichment at this feature; and (vii) genes with this feature exhibit unique dinucleotide distributions at the intron-exon boundary. The NOL scores point toward a physical property of DNA that may play a role in the mechanism of pre-mRNA splicing. These results provide a foundation for identification of a new set of regulatory DNA elements involved in splicing regulation.

Exon-Intron Boundary Detection Made Easy by Physicochemical Properties of DNA

“…Unfortunately, these tools, too, fall short when it comes to annotating splice junctions in DNA sequences 24,25,26,27,28 . Recent exploration of chromatin organization and nucleosome positioning approach presents a fresh perspective 29 . It has yet to achieve the desired level of sensitivity and speci city.…”

Intron exon boundary junctions in human genome have in-built unique structural and energetic signals

“…Some currently available splice-junction prediction tools identify exon–intron boundaries in mRNA sequences, for organisms with reference genome ( 18–21 ) as well as without a reference genome ( 22 ), but these tools are unable to annotate splice junctions in DNA sequence. Recently, role of chromatin organization and nucleosome positioning as determinant of exon–intron boundary was also investigated; though it looks at the problem with a new angle, satisfactory level of sensitivity and specificity could not be achieved ( 23 ). Despite the many insights resulting from such studies over the years, it is apparent that our conceptual frameworks are not adequate yet.…”