Exonic splicing code and coordination of divalent metals in proteins

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Exonic sequences harbor crucial protein-coding and RNA splicing information.
• The interplay between protein and splicing codes is complex and not fully understood.
• Divalent metal ions are essential for metalloprotein function, with varying coordination preferences.

Purpose of the Study:

• To investigate the splicing codes of human exons encoding residues for divalent metal ion coordination.
• To compare the splicing support for exons coordinating calcium (Ca2+) versus zinc (Zn2+).
• To understand how RNA splicing ensures metalloprotein expression.

Main Methods:

• Analysis of traditional and auxiliary splicing codes in human exons.
• Comparison of splicing motifs and splice site strengths for Ca2+- and Zn2+-coordinating exons.
• Assessment of exon splicing patterns across multiple tissues.

Main Results:

• Exons encoding Zn2+-coordinating amino acids receive less support from auxiliary splicing motifs compared to Ca2+-coordinating exons.
• This deficit is compensated by stronger splice sites and richer polypyrimidine tracts in Zn2+ exons.
• Both Ca2+ and Zn2+ exons demonstrate near-constitutive splicing across various tissues.

Conclusions:

• Metal coordination requirements influence RNA splicing patterns.
• The plasticity of exon-intron architecture effectively overcomes splicing constraints for essential metalloproteins.
• Efficient metalloprotein expression is maintained through adaptive splicing mechanisms.