Natural antisense RNA inhibits the expression of BCMA, a tumour necrosis factor receptor homologue.

Overexpression of both p12 and p12-ATG antisense BCMA resulted in a large decrease in the amount of BCMA protein produced, with no change in BCMA RNA levels, indicating that BCMA expression is regulated by antisense BCMA RNA at the translational level. We have also observed slight adenosine modifications, suggestive of the activity of a double-stranded RNA-specific adenosine deaminase.These data suggest that antisense BCMA may operate under physiological conditions using similar antisense-mediated control mechanisms, to inhibit the expression of the BCMA gene.BCMA (B-cell maturation) belongs to the tumour necrosis factor receptor (TNFR) gene family [1], and is specifically expressed in mature B lymphocytes [2,3]. BCMA and TACI (transmembrane activator and CAML-interactor), another TNFR-homologue [4], bind two TNF-homologues; BAFF (also called TALL-1, THANK, BLyS, and zTNF4) [5-9] and APRIL [10]. Futhermore, BAFF can bind to a third receptor BAFF-R which is specific to this ligand.[11,12]. This defines a complexe ligand-receptor system that may play an important role in B lymphocyte differentiation [9,13-18] and in the regulation of B-cell function.Naturally occurring antisense RNAs in eukaryotes may regulate sense gene expression, acting at the transcriptional, post-transcriptional or translational level [19]. We have previously reported the presence of a natural antisense BCMA RNA, which is produced by transcription from the same locus as BCMA and has typical mRNA features, e.g. polyadenylation, splicing, Kozak consensus sequence and an open reading frame encoding a 115 amino acid peptide (p12) [20]. RNase protection assays demonstrated the simultaneous presence of natural sense and antisense BCMA transcripts in most of the human B-cell lines and lymphoid tissues tested. We have not succeded to evidence antisense-BCMA transcripts in mouse B lymphocytes. In this study, we investigated whether antisense BCMA RNA regulated the expression of sense BCMA. We observed an