The Expression of Tubulin Cofactor A (TBCA) Is Regulated by a Noncoding Antisense Tbca RNA during Testis Maturation

Background Recently, long noncoding RNAs have emerged as pivotal molecules for the regulation of coding genes' expression. These molecules might result from antisense transcription of functional genes originating natural antisense transcripts (NATs) or from transcriptional active pseudogenes. TBCA interacts with β-tubulin and is involved in the folding and dimerization of new tubulin heterodimers, the building blocks of microtubules. Methodology/Principal Findings We found that the mouse genome contains two structurally distinct Tbca genes located in chromosomes 13 ( Tbca 13) and 16 ( Tbca 16). Interestingly, the two Tbca genes albeit ubiquitously expressed, present differential expression during mouse testis maturation. In fact, as testis maturation progresses Tbca 13 mRNA levels increase progressively, while Tbca 16 mRNA levels decrease. This suggests a regulatory mechanism between the two genes and prompted us to investigate the presence of the two proteins. However, using tandem mass spectrometry we were unable to identify the TBCA16 protein in testis extracts even in those corresponding to the maturation step with the highest levels of Tbca 16 transcripts. These puzzling results led us to re-analyze the expression of Tbca 16. We then detected that Tbca 16 transcription produces sense and natural antisense transcripts. Strikingly, the specific depletion by RNAi of these transcripts leads to an increase of Tbca 13 transcript levels in a mouse spermatocyte cell line. Conclusions/Significance Our results demonstrate that Tbca 13 mRNA levels are post-transcriptionally regulated by the sense and natural antisense Tbca 16 mRNA levels. We propose that this regulatory mechanism operates during spermatogenesis, a process that involves microtubule rearrangements, the assembly of specific microtubule structures and requires critical TBCA levels.