Alternative Processing of the Human FMO6 Gene Renders Transcripts Incapable of Encoding a Functional Flavin-Containing Monooxygenase
The flavin-containing monooxygenases (FMOs) are a family of five microsomal enzymes important for the oxidative metabolism of environmental toxicants, natural products, and therapeutics. With the exception of FMO5, the FMO are encoded within a single gene cluster on human chromosome 1q23â25. As pa...
Gespeichert in:
Veröffentlicht in: | Molecular pharmacology 2002-08, Vol.62 (2), p.320-325 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | The flavin-containing monooxygenases (FMOs) are a family of five microsomal enzymes important for the oxidative metabolism
of environmental toxicants, natural products, and therapeutics. With the exception of FMO5, the FMO are encoded within a single
gene cluster on human chromosome 1q23â25. As part of the human genome effort, an FMO -like gene, FMO6 , was identified between FMO3 and FMO2 (GenBank accession no. ALO21026 ). Sequence analysis of this putative FMO family member revealed nothing that would a priori argue against a functional gene and encoded protein. When FMO6 expression was examined by reverse transcriptase coupled polymerase chain reaction DNA amplification, transcripts were identified
in 8 of 11 human liver samples, but 0 of 4 kidney biopsy samples. However, in all cases, the observed transcripts were shorter
than predicted. Sequence analysis revealed skipping of exon 4, exons 3 and 4, and/or the use of alternative splice donor or
acceptor sites in introns 3, 4, 6, and 8, resulting in nine unique transcripts. Based on an analysis of possible open reading
frames, none of these transcripts would encode a functional FMO enzyme. Taking advantage of the high sequence identity between
FMO3 and FMO6 , it is posited that the loss of binding sites for the serine-arginineârich splicing factor protein family within exons 3
and 4 contributes to the exon skipping events, although the most commonly observed alternative splice event results from a
21-bp insertion immediately 3â² to the predicted FMO6 intron 8 splice acceptor site, diminishing the efficiency of this site. |
---|---|
ISSN: | 0026-895X 1521-0111 |
DOI: | 10.1124/mol.62.2.320 |