Novel isoforms of the fragile X related protein FXR1P are expressed during myogenesis

The fragile X syndrome results from transcriptional silencing of the FMR1 gene and the absence of its encoded FMRP protein, Two autosomal homologues of the FMR1 gene, FXR1 and FXR2, have been identified and the overall structures of the corresponding proteins am very similar to that of FMRP, Using antibodies raised against FXR1P, we observed that two major protein isoforms of relative MW of 78 and 70 kDa are expressed in different mammalian cell lines and in the majority of mouse tissues. In mammalian cells grown in culture as well as in brain extracts, both P-78 and P-70 isoforms are associated with mRNPs within translating poly; ribosomes, Similarly to their closely related FMRP homologues, In muscle tissues as well as in murine myoblastic cell lines induced to differentiate into myotubes, FXR1P(78) and P-70 isoforms are replaced by novel unpredicted isoforms of 81-84 kDa and a novel FXR1 exon splice variant was detected in muscle RNA. While P81-84 isoforms expressed after fusion into myotubes in murine myoblast cell lines grown in culture: am associated with polyribosomes, this is not the case when isolated from muscle tissues since they sediment with lower S values. Immunohistochemical studies showed coexpression of FMRP and FXR1P(70) and P-78 in the cytoplasm of brain neurons, while in muscle no FMRP was detected and FXR1P(81-84) were mainly localized to structures within the muscle contractile bands. The complex expression pattern of FXR1P suggests tissue-specific expression for the various isoforms of FXR1 and the differential expression of FMRP and FXR1 Ps suggests that in certain types of cells and tissues, complementary functions may be fulfilled by the various FMRP family members.