Location: Warmwater Aquaculture Research UnitTitle: Processing of fish lg heavy chain transcripts diverse splicing patterns and unusual nonsense mediated decay) Author
Submitted to: Developmental and Comparative Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/29/2010
Publication Date: 7/1/2011
Citation: Quiniou, S., Wilson, M., Boudinot, P. 2011. Processing of fish lg heavy chain transcripts: Diverse splicing patterns and unusual nonsense mediated decay. Developmental and Comparative Immunology. 35:949-958. Interpretive Summary: Immunoglobulins (or antibodies) are critical component of the vertebrate immune system to identify and neutralize pathogens. This article describes the pathway creating diverse forms of immunoglobulin molecules supporting specific (effective) function of the antibody. Understanding the genesis of these different immunoglobulin forms in fish is instrumental for the development of diagnostic tools and will help the design of better vaccines and monitoring of fish health.
Technical Abstract: Alternate pathways of RNA processing play an important role in the expression of the secreted (S) and membrane (Mb) forms of immunoglobulin (Ig) heavy (H) chain isotypes in all vertebrates. Interestingly, while the differential splicing mechanism and the splice sites that generate the two forms of Ig are conserved in mammals, this conservation is not observed in the different fish species. For example, in mammals, amphibians, and sharks mRNAs encoding Mb IgM are made by splicing of the first transmembrane (TM) encoding exon into a cryptic donor site near the 3' end of the constant (C)'4 exon. In contrast, teleost fish splice the first TM exon 1 into directly to the 3' splice donor site of the C'3 exon and chondrostean and holostean fish exhibit a diverse usage of alternative splice sites which leads to expression of different Mb IgM H chain sizes in these species. Also, in all teleost examined to date, Mb IgD is considered chimeric since the Ig' chain is produced by alternative mRNA splicing and consist of a rearranged VDJ, spliced to C'1, the C' exons and the Ig' TM. This inclusion of C'1 is also observed with common carp IgT transcripts. Together, these observations raise questions on how different fish regulate alternative RNA splicing and if their splicing machinery is more complex. Here a preliminary scan of the zebrafish and stickleback genomes provide evidence that gene orthologs of the mammalian main splice factors are highly conserved and maintained as single copy genes, while the snRNPs U repertoire may be different.