Differential domain evolution and complex RNA processing in a family of paralogous EPB41 (protein 4.1) genes facilitate expression of diverse tissue-specific isoforms.
The EPB41 (protein 4.1) genes epitomize the resourcefulness of the mammalian genome to encode a complex proteome from a small number of genes. By utilizing alternative transcriptional promoters and tissue-specific alternative pre-mRNA splicing, EPB41, EPB41L2, EPB41L3, and EPB41L1 encode a diverse array of structural adapter proteins. Comparative genomic and transcript analysis of these 140- to 240-kb genes indicates several unusual features: differential evolution of highly conserved exons encoding known functional domains interspersed with unique exons whose size and sequence variations contribute substantially to intergenic diversity; alternative first exons, most of which map far upstream of the coding regions; and complex tissue-specific alternative pre-mRNA splicing that facilitates synthesis of functionally different complements of 4.1 proteins in various cells. Understanding the splicing regulatory networks that control protein 4.1 expression will be critical to a full appreciation of the many roles of 4.1 proteins in normal cell biology and their proposed roles in human cancer.
Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Marilyn
M
Parra
Sherry
S
Gee
Nadine
N
Chan
Dmitriy
D
Ryaboy
Inna
I
Dubchak
Narla
N
Mohandas
Philippe D
PD
Gascard
John G
JG
Conboy
D017398:Alternative Splicing; D000818:Animals; D005075:Biological Evolution; D001798:Blood Proteins / Q000235:genetics*; D003598:Cytoskeletal Proteins; D005091:Exons; D006801:Humans; D007438:Introns; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012322:RNA Precursors / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D012322:RNA Precursors; D012333:RNA, Messenger; C488402:Epb41l3 protein, mouse; C028841:erythrocyte membrane band 4.1 protein; C116887:EPB41L3 protein, human