Natural antisense transcript of natriuretic peptide precursor A (NPPA): structural organization and modulation of NPPA expression.
BACKGROUND
Mammalian transcriptome contains a large proportion of diverse and structurally complex noncoding RNAs. One class of such RNAs, natural antisense transcripts (NATs), are derived from the opposite strand of many protein-coding genes. Although the exact structure and functional relevance of most of the NATs is unknown, their emerging role as gene expression regulators raises the hypothesis that NATs might contribute to development of complex human disorders. The goal of our study was to investigate the involvement of NATs in regulation of candidate genes for blood pressure.


RESULTS
First we analysed blood pressure candidate genes for the presence of natural antisense transcripts. In silico analysis revealed that seven genes (ADD3, NPPA, ATP1A1, NPR2, CYP17A1, ACSM3, SLC14A2) have an antisense partner transcribed from the opposite strand. We characterized NPPA and its antisense transcript (NPPA-AS) in more detail. We found that NPPA-AS is expressed in a number of human tissues as a collection of alternatively spliced isoforms and that NPPA-AS and NPPA can form RNA duplexes in vivo. We also demonstrated that a specific NPPA-AS isoform is capable of down-regulating the intron-retained NPPA mRNA variant. We studied the evolutionary conservation of NPPA-AS and were able to detect the presence of Nppa-as transcript in mouse.


CONCLUSIONS
Our results demonstrate functional interaction of NPPA-AS with NPPA at the RNA level and suggest that antisense transcription might be an important post-transcriptional mechanism modulating NPPA expression.
Annilo
Tarmo
T
Institute of Molecular and Cell Biology, University of Tartu, 51010 Tartu, Estonia. tarmo.annilo@ut.ee
Kepp
Katrin
K
Laan
Maris
M
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics* / Q000378:metabolism; D001794:Blood Pressure; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D020098:Natriuretic Peptide, C-Type / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing; D016372:RNA, Antisense / Q000235:genetics* / Q000378:metabolism
C472955:NPPA protein, human; C431578:Nppa protein, mouse; D020033:Protein Isoforms; D011498:Protein Precursors; D016372:RNA, Antisense; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor