A new cancer-testis long noncoding RNA, the OTP-AS1 RNA

Abstract Orthopedia homeobox ( OTP ) gene encodes a homeodomain-containing transcription factor involved in brain development. OTP is mapped to human chromosome 5q14.1. Earlier we described transcription in the second intron of this gene in wide variety of tumors, but among normal tissues only in testis. In GeneBank these transcripts are presented by several 300-400 nucleotides long AI267901-like ESTs. We assumed that AI267901-like ESTs belong to longer transcript(s). We used the Rapid Amplification of cDNA Ends (RACE) approach and other methods to find the full-length transcript. The found transcript was 2436 nucleotides long polyadenylated sequence in antisense to OTP gene. The corresponding gene consisted of two exons separated by an intron of 2961 bp long. The first exon was found to be 91 bp long and located in the third exon of OTP gene. The second exon was 2345bp long and located in the second intron of OTP gene. The search of possible open reading frames (ORFs) showed the lack of significant ORFs. We have shown the expression of new gene in many human tumors and only in one sampled normal testis. The data suggest that we discovered a new antisense cancer-testis sequence OTP - AS1 ( OTP - antisense RNA 1), which belongs to long noncoding RNAs (lncRNAs). According to our findings we assume that OTP-AS1 and OTP genes may be the CT-coding gene/CT-ncRNA pair involved in regulatory interactions. Author summary Previously, long non-coding RNAs (lncRNAs) were considered as genetic “noise”. However, it was later shown that only 2% of genomic transcripts have a protein-coding ability. Non-coding RNA is divided into short non-coding RNAs (20-200 nucleotides) and long noncoding RNAs (200-100,000 nucleotides). Genes encoding lncRNA often overlap or are adjacent to protein-coding genes, and localization of this kind is beneficial in order to regulate the transcription of neighboring genes. Studies have shown that of lncRNAs play many roles in the regulation of gene expression. New evidence indicates that dysfunctions of lncRNAs are associated with human diseases and cancer. In our study we found a new cancer-testis long noncoding RNA ( OTP-AS1 ), which is an antisense of protein-coding cancer-testis gene ( OTP ). Thus, OTP-AS1 and OTP genes may be the CT-coding gene/CT-ncRNA pair involved in regulatory interactions. This is supported by the similar profile of their expression. OTP-AS1 may be of interest as a potential diagnostic marker of cancer or a potential target for cancer therapy. Part of OTP-AS1 gene (5’-end of the second exon) is evolutionary younger than the rest of gene sequence and is less conservative. This links OTP-AS1 gene with so-called TSEEN (tumor-specifically expressed, evolutionary novel) genes described by the authors in previous papers.