title: The expression of tubulin cofactor A (TBCA) is regulated by a noncoding antisense Tbca RNA during testis maturation.
abstract: 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.
  
  
  RESULTS
  We found that the mouse genome contains two structurally distinct Tbca genes located in chromosomes 13 (Tbca13) and 16 (Tbca16). Interestingly, the two Tbca genes albeit ubiquitously expressed, present differential expression during mouse testis maturation. In fact, as testis maturation progresses Tbca13 mRNA levels increase progressively, while Tbca16 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 Tbca16 transcripts. These puzzling results led us to re-analyze the expression of Tbca16. We then detected that Tbca16 transcription produces sense and natural antisense transcripts. Strikingly, the specific depletion by RNAi of these transcripts leads to an increase of Tbca13 transcript levels in a mouse spermatocyte cell line.
  
  
  CONCLUSIONS
  Our results demonstrate that Tbca13 mRNA levels are post-transcriptionally regulated by the sense and natural antisense Tbca16 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.
authors.affiliation: Departamento de Biología Molecular, Facultad de Medicina, IFIMAV-Universidad de Cantabria, Santander, Spain.
authors.forename: Sofia
authors.initials: S
authors.lastname: Nolasco
authors.forename: Javier
authors.initials: J
authors.lastname: Bellido
authors.forename: João
authors.initials: J
authors.lastname: Gonçalves
authors.forename: Alexandra
authors.initials: A
authors.lastname: Tavares
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Zabala
authors.forename: Helena
authors.initials: H
authors.lastname: Soares
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D033481:Chromosomes, Mammalian / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D016678:Genome / Q000235:genetics; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016372:RNA, Antisense / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D013090:Spermatocytes / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics; D013737:Testis / Q000254:growth & development* / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D016372:RNA, Antisense; D012333:RNA, Messenger; D022661:RNA, Untranslated; C577218:TBCA protein, mouse