Alternative splicing in human transcriptome: Functional and structural influence on proteins

Kei Yura, Masafumi Shionyu, Kei Hagino, Atsushi Hijikata, Yoshinori Hirashima, Taku Nakahara, Tatsuya Eguchi, Kazuki Shinoda, Akihiro Yamaguchi, Ken ichi Takahashi, Takeshi Itoh, Tadashi Imanishi, Takashi Gojobori, Mitiko Go

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45 Citations (Scopus)

Abstract

Alternative splicing is a molecular mechanism that produces multiple proteins from a single gene, and is thought to produce variety in proteins translated from a limited number of genes. Here we analyzed how alternative splicing produced variety in protein structure and function, by using human full-length cDNAs on the assumption that all of the alternatively spliced mRNAs were translated to proteins. We found that the length of alternatively spliced amino acid sequences, in most cases, fell into a size shorter than that of average protein domain. We evaluated comprehensively the presumptive three-dimensional structures of the alternatively spliced products to assess the impact of alternative splicing on gene function. We found that more than half of the products encoded proteins which were involved in signal transduction, transcription and translation, and more than half of alternatively spliced regions comprised interaction sites between proteins and their binding partners, including substrates, DNA/RNA, and other proteins. Intriguingly, 67% of the alternatively spliced isoforms showed significant alterations to regions of the protein structural core, which likely resulted in large conformational change. Based on those findings, we speculate that there are a large number of cases that alternative splicing modulates protein networks through significant alteration in protein conformation.

Original languageEnglish
Pages (from-to)63-71
Number of pages9
JournalGene
Volume380
Issue number2
DOIs
Publication statusPublished - 2006 Oct 1
Externally publishedYes

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Keywords

  • Exon-intron structure
  • Full-length cDNA
  • Gene function
  • Protein stability
  • Signaling pathway
  • Three-dimensional structure

ASJC Scopus subject areas

  • Genetics

Cite this

Yura, K., Shionyu, M., Hagino, K., Hijikata, A., Hirashima, Y., Nakahara, T., Eguchi, T., Shinoda, K., Yamaguchi, A., Takahashi, K. I., Itoh, T., Imanishi, T., Gojobori, T., & Go, M. (2006). Alternative splicing in human transcriptome: Functional and structural influence on proteins. Gene, 380(2), 63-71. https://doi.org/10.1016/j.gene.2006.05.015