Conserved alternative splicing and expression patterns of arthropod N-Cadherin

Shu Ning Hsu, Shinichi Yonekura, Chun Yuan Ting, Hugh M. Robertson, Youichi Iwai, Tadashi Uemura, Chi Hon Lee, Akira Chiba

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Metazoan development requires complex mechanisms to generate cells with diverse function. Alternative splicing of premRNA not only expands proteomic diversity but also provides a means to regulate tissue-specific molecular expression. The N-Cadherin gene in Drosophila contains three pairs of mutually-exclusive alternatively-spliced exons (MEs). However, no significant differences among the resulting protein isoforms have been successfully demonstrated in vivo. Furthermore, while the N-Cadherin gene products exhibit a complex spatiotemporal expression pattern within embryos, its underlying mechanisms and significance remain unknown. Here, we present results that suggest a critical role for alternative splicing in producing a crucial and reproducible complexity in the expression pattern of arthropod N-Cadherin. We demonstrate that the arthropod N-Cadherin gene has maintained the three sets of MEs for over 400 million years using in silico and in vivo approaches. Expression of isoforms derived from these MEs receives precise spatiotemporal control critical during development. Both Drosophila and Tribolium use ME-13a and ME-13b in "neural" and "mesodermal" splice variants, respectively. As proteins, either ME-13a- or ME-13b-containing isoform can cell-autonomously rescue the embryonic lethality caused by genetic loss of N-Cadherin. Ectopic muscle expression of either isoform beyond the time it normally ceases leads to paralysis and lethality. Together, our results offer an example of well-conserved alternative splicing increasing cellular diversity in metazoans.

Original languageEnglish
JournalPLoS Genetics
Volume5
Issue number4
DOIs
StatePublished - Apr 1 2009

Fingerprint

Arthropods
cadherins
alternative splicing
Alternative Splicing
Cadherins
arthropod
arthropods
Protein Isoforms
gene
protein
proteomics
metazoan
Drosophila
embryo
Tribolium
Genes
muscle
protein isoforms
genes
paralysis

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Conserved alternative splicing and expression patterns of arthropod N-Cadherin. / Hsu, Shu Ning; Yonekura, Shinichi; Ting, Chun Yuan; Robertson, Hugh M.; Iwai, Youichi; Uemura, Tadashi; Lee, Chi Hon; Chiba, Akira.

In: PLoS Genetics, Vol. 5, No. 4, 01.04.2009.

Research output: Contribution to journalArticle

Hsu, SN, Yonekura, S, Ting, CY, Robertson, HM, Iwai, Y, Uemura, T, Lee, CH & Chiba, A 2009, 'Conserved alternative splicing and expression patterns of arthropod N-Cadherin', PLoS Genetics, vol. 5, no. 4. https://doi.org/10.1371/journal.pgen.1000441
Hsu, Shu Ning ; Yonekura, Shinichi ; Ting, Chun Yuan ; Robertson, Hugh M. ; Iwai, Youichi ; Uemura, Tadashi ; Lee, Chi Hon ; Chiba, Akira. / Conserved alternative splicing and expression patterns of arthropod N-Cadherin. In: PLoS Genetics. 2009 ; Vol. 5, No. 4.
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