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Exonic splicing code and coordination of divalent metals in proteins

Exonic splicing code and coordination of divalent metals in proteins
Exonic splicing code and coordination of divalent metals in proteins
Exonic sequences contain both protein-coding and RNA splicing information but the interplay of the protein and splicing code is complex and poorly understood. Here, we have studied traditional and auxiliary splicing codes of human exons that encode residues coordinating two essential divalent metals at the opposite ends of the Irving–Williams series, a universal order of relative stabilities of metal–organic complexes. We show that exons encoding Zn2+-coordinating amino acids are supported much less by the auxiliary splicing motifs than exons coordinating Ca2+. The handicap of the former is compensated by stronger splice sites and uridine-richer polypyrimidine tracts, except for position –3 relative to 3′ splice junctions. However, both Ca2+ and Zn2+ exons exhibit close-to-constitutive splicing in multiple tissues, consistent with their critical importance for metalloprotein function and a relatively small fraction of expendable, alternatively spliced exons. These results indicate that constraints imposed by metal coordination spheres on RNA splicing have been efficiently overcome by the plasticity of exon–intron architecture to ensure adequate metalloprotein expression.
0305-1048
Bakhtiar, Dara
45f8af67-49d0-44a7-9f99-10c681b5ba76
Vondraskova, Katarina
88e48681-1ea7-4843-95e7-95ca2aa4c89c
Pengelly, Reuben J.
af97c0c1-b568-415c-9f59-1823b65be76d
Chivers, Martin
639fadfe-5293-45eb-8c38-22cbbf3f4b68
Kralovicova, Jana
b3e0c1e7-05ed-445d-b3d9-ace11e3b4878
Vorechovsky, Igor
7245de2f-8c9b-4034-8935-9a451d9b682e
Bakhtiar, Dara
45f8af67-49d0-44a7-9f99-10c681b5ba76
Vondraskova, Katarina
88e48681-1ea7-4843-95e7-95ca2aa4c89c
Pengelly, Reuben J.
af97c0c1-b568-415c-9f59-1823b65be76d
Chivers, Martin
639fadfe-5293-45eb-8c38-22cbbf3f4b68
Kralovicova, Jana
b3e0c1e7-05ed-445d-b3d9-ace11e3b4878
Vorechovsky, Igor
7245de2f-8c9b-4034-8935-9a451d9b682e

Bakhtiar, Dara, Vondraskova, Katarina, Pengelly, Reuben J., Chivers, Martin, Kralovicova, Jana and Vorechovsky, Igor (2023) Exonic splicing code and coordination of divalent metals in proteins. Nucleic Acids Research. (doi:10.1093/nar/gkad1161).

Record type: Article

Abstract

Exonic sequences contain both protein-coding and RNA splicing information but the interplay of the protein and splicing code is complex and poorly understood. Here, we have studied traditional and auxiliary splicing codes of human exons that encode residues coordinating two essential divalent metals at the opposite ends of the Irving–Williams series, a universal order of relative stabilities of metal–organic complexes. We show that exons encoding Zn2+-coordinating amino acids are supported much less by the auxiliary splicing motifs than exons coordinating Ca2+. The handicap of the former is compensated by stronger splice sites and uridine-richer polypyrimidine tracts, except for position –3 relative to 3′ splice junctions. However, both Ca2+ and Zn2+ exons exhibit close-to-constitutive splicing in multiple tissues, consistent with their critical importance for metalloprotein function and a relatively small fraction of expendable, alternatively spliced exons. These results indicate that constraints imposed by metal coordination spheres on RNA splicing have been efficiently overcome by the plasticity of exon–intron architecture to ensure adequate metalloprotein expression.

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Accepted/In Press date: 17 November 2023
Published date: 6 December 2023

Identifiers

Local EPrints ID: 485447
URI: http://eprints.soton.ac.uk/id/eprint/485447
ISSN: 0305-1048
PURE UUID: b4a64168-18ea-488f-b01f-8506fe30f567
ORCID for Reuben J. Pengelly: ORCID iD orcid.org/0000-0001-7022-645X
ORCID for Martin Chivers: ORCID iD orcid.org/0000-0001-8581-2670
ORCID for Igor Vorechovsky: ORCID iD orcid.org/0000-0002-6740-6502

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Date deposited: 06 Dec 2023 17:48
Last modified: 31 Jul 2024 01:46

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Contributors

Author: Dara Bakhtiar
Author: Katarina Vondraskova
Author: Martin Chivers ORCID iD
Author: Jana Kralovicova

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