Splice-mediated insertion of an Alu sequence inactivates ornithine delta-aminotransferase: a role for Alu elements in human mutation.

作者：Grant A. Mitchell, Damian Labuda, G Fontaine, Jean Marie Saudubray, Jean‐Paul Bonnefont, Stanislas Lyonnet, Lawrence C. Brody, Gary Daniel Steel, Cassandra Obie, David Valle · 发表于：Proceedings of the National Academy of Sciences · 年份：1991 · DOI：10.1073/pnas.88.3.815 · 被引用次数：140 · 研究领域：Amino Acid Enzymes and Metabolism、Advanced biosensing and bioanalysis techniques、RNA and protein synthesis mechanisms

In studies of mutations causing deficiency of ornithine delta-aminotransferase (EC 2.6.1.13), we found an allele whose mature mRNA has a 142-nucleotide insertion at the junction of sequences from exons 3 and 4. The insert derives from an Alu element in ornithine delta-aminotransferase intron 3 oriented in the direction opposite to transcription (an "antisense Alu"). A guanine----cytosine transversion creates a donor splice site in this Alu, activating a cryptic acceptor splice site at its 5' end and causing splice-mediated insertion of an Alu fragment into the mature ornithine-delta-aminotransferase mRNA. We note that the complement of the Alu consensus sequence has at least two cryptic acceptor sites and several potential donor sequences and predict that similar mutations will be found in other genes.