Natural antisense transcripts enhance bone formation by increasing sense IFITM5 transcription.

Interferon induced transmembrane protein 5 (IFITM5) has been recognized as an osteoblast differentiation factor. Its regulation, however, is still unclear. In this report, four novel naturally occurring antisense transcripts of rat IFITM2 and IFITM5 transcribed from the opposite strand of the IFITM gene locus, were isolated and characterized. They are alternatively transcribed from rat chromosome 1 and expressed at relatively high levels during early differentiation of primary isolates of rat osteoblast cells. There are two common fragments in all of the isoform cDNA sequences that are complimentary to both IFITM2 and IFITM5 respectively. There is an additional unique region in one isoform, immediately downstream of the putative IFITM5 complimentary region, which is also complimentary to IFITM cDNA sequence. Reading frame analysis showed that these antisense transcripts are non protein coding mRNAs. We investigated the expression of these antisense transcripts and their effects on IFITM expression as well as osteoblast differentiation. All isoforms were positively correlated with IFITM5 expression and antisense specific siRNAs inhibited osteoblast differentiation significantly. In contrast, these antisense transcripts had no effect on the expression of IFITM2. We speculate that IFITM5 may be regulated by antisense transcripts.