Abstract
Previous studies have reported > 10 kilobases of human fibrillin-1 cDNA sequence, but a consensus regarding the 5' end of the transcript remains to be worked out. One approach to developing a clear consensus would be to search for regions of evolutionary conservation in transcripts from a related species such as mouse. As reported here, the mouse fibrillin-1 transcript encodes a highly conserved polypeptide of 2,871 amino acids. The upstream sequence that flanks the ATG is considerably less well conserved, however. Indeed, the ATG codon (which occurs in the context of a Kozak consensus sequence and is located just upstream of a consensus signal peptide) signals the point where human and mouse fibrillin-1 sequences cease to be nearly identical. Together, these results are consistent with previous efforts by Pereira et al. (Pereira, L., D'Alessio, M., Ramirez, F., Lynch, J. R., Sykes, B., Pangilinan, T., and Bonadio, J. (1993) Human Mol. Genet. 2, 961-968) to identify the human fibrillin-1 translational start site. Sequences immediately upstream of the ATG are GC-rich and devoid of TATA and CCAAT boxes, which suggests that the mouse fibrillin-1 gene will be broadly expressed. A survey of expression in mouse embryo tissues is consistent with this hypothesis and suggests two novel functions for fibrillin-associated microfibrils in non-elastic connective tissues.
Highlights
Previous studies have reported > 10 kilobases of human fibrillin-l eDNA sequence, but a consensus regarding the 5' end of the transcript remains to be worked out
A survey of expression in mouse embryo tissues is consistent with this hypothesis and suggests two novel functions for fibrillin-associated microfibrils in non-elastic connective tissues
35-kDa protein isolated from bovine ligamentum nuchae (Serafini-Fracassini et al, 1981), proteins of 78, 70, and 25 kDa (Gibson et al, 1989), and a 58-kDa protein that is post-translationally modified into a 32-kDa fragment called the associated microfibril protein (Horrigan et al, 1992)
Summary
Dept. of Pathology, University of Michigan, MSRB I, Rm. 3510, 1150 W. A limited analysis suggested that sequences upstream of the cap site were GC-rich and lacked TATA and CCAAT boxes The study by Corson et al (1993) has raised important questions about the structure of the FBN-l transcript that bear on normal connective tissue function as well as the pathogenesis of Marfan syndrome and related disorders. The mouse embryo and human fibrillin-1 transcript share a remarkable >95% DNA and amino acid sequence identity, extending 8,613 nt downstream of the initiator Met codon identified by Pereira et at. A survey of the expression pattern of the fibrillin-1 transcript suggests a novel role for fibrillin-associated microfibrils during cardiac morphogenesis and during connective tissue remodeling of uterine stroma after embryo implantation
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