The gene structure and expression of human ABHD1: overlapping polyadenylation signal sequence with Sec12.
BACKGROUND
Overlapping sense/antisense genes orientated in a tail-to-tail manner, often involving only the 3'UTRs, form the majority of gene pairs in mammalian genomes and can lead to the formation of double-stranded RNA that triggers the destruction of homologous mRNAs. Overlapping polyadenylation signal sequences have not been described previously.


RESULTS
An instance of gene overlap has been found involving a shared single functional polyadenylation site. The genes involved are the human alpha/beta hydrolase domain containing gene 1 (ABHD1) and Sec12 genes. The nine exon human ABHD1 gene is located on chromosome 2p23.3 and encodes a 405-residue protein containing a catalytic triad analogous to that present in serine proteases. The Sec12 protein promotes efficient guanine nucleotide exchange on the Sar1 GTPase in the ER. Their sequences overlap for 42 bp in the 3'UTR in an antisense manner. Analysis by 3' RACE identified a single functional polyadenylation site, ATTAAA, within the 3'UTR of ABHD1 and a single polyadenylation signal, AATAAA, within the 3'UTR of Sec12. These polyadenylation signals overlap, sharing three bp. They are also conserved in mouse and rat. ABHD1 was expressed in all tissues and cells examined, but levels of ABHD1 varied greatly, being high in skeletal muscle and testis and low in spleen and fibroblasts.


CONCLUSIONS
Mammalian ABHD1 and Sec12 genes contain a conserved 42 bp overlap in their 3'UTR, and share a conserved TTTATTAAA/TTTAATAAA sequence that serves as a polyadenylation signal for both genes. No inverse correlation between the respective levels of ABHD1 and Sec12 RNA was found to indicate that any RNA interference occurred.
Department of Clinical and Diagnostic Oral Science, Clinical Research Centre, Queen Mary, University of London, 2 Newark Street, London, E1 2AD, UK. a.j.edgar@qmul.ac.uk
Alasdair J
AJ
Edgar
D000328:Adult; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002265:Carboxylic Ester Hydrolases; D019295:Computational Biology / Q000379:methods / Q000706:statistics & numerical data; D016373:DNA, Antisense / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005807:Genes, Overlapping / Q000235:genetics*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D008168:Lung / Q000201:enzymology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D010053:Ovary / Q000201:enzymology; D011467:Prostate / Q000201:enzymology; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D039104:RNA 3' Polyadenylation Signals / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*; D014157:Transcription Factors
D016373:DNA, Antisense; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; C118971:PREB protein, human; C485591:Preb protein, mouse; C485592:Preb protein, rat; D014157:Transcription Factors; D012313:RNA; D006867:Hydrolases; C454239:LABH1, mouse; C476001:ABHD1 protein, human; D002265:Carboxylic Ester Hydrolases; D012697:Serine Endopeptidases