Alternate pre-mRNA processing pathways in the production of membrane IgM heavy chains in holostean fish

Abstract

A single gene encodes two forms of the IgM heavy chain (μ) in vertebrates: one (μs) present in serum as secreted IgM and the other (μm) as the antigen receptor form of IgM present on the B-lymphocyte membrane. The mRNAs encoding μs and μm are derived from a single primary transcript by alternate path-ways of RNA processing. In all vertebrates so far examined, with the exception of teleosts, μm mRNA is produced by splicing the transmembrane (TM) encoding exon 1 into a cryptic donor site near the 3′ end of the Cμ4 exon. In contrast, teleost species splice the TM exon 1 into the regular splice donor site at the 3′ boundary of the Cμ3 exon. We have examined μm mRNAs in two species of primitive bony fish, the holostean bowfin and the longnose gar. These fish utilize both the Cμ3 to TM1 (teleost) pathway and the typical cryptic Cμ4 to TM1 pathway. In addition the bowfin possesses a cryptic splice donor site near the middle of Cμ3. This is used in the production of a third species of μm-encoding mRNA, but does not participate in the production of an alternate form of the μs mRNA. The structure and patterns of expression of their μ genes suggest that the gar and bowfin may be more closely related than implied by the current view of fish evolution.