Natural antisense transcription from a comparative perspective

Genomics. 2016 Aug;108(2):56-63. doi: 10.1016/j.ygeno.2016.05.004. Epub 2016 May 27.


Natural antisense transcripts (NATs) can interfere with the expression of complementary sense transcripts with exquisite specificity. We have previously cloned NATs of Slc34a loci (encoding Na-phosphate transporters) from fish and mouse. Here we report the cloning of a human SLC34A1-related NAT that represents an alternatively spliced PFN3 transcript (Profilin3). The transcript is predominantly expressed in testis. Phylogenetic comparison suggests two distinct mechanisms producing Slc34a-related NATs: Alternative splicing of a transcript from a protein coding downstream gene (Pfn3, human/mouse) and transcription from the bi-directional promoter (Rbpja, zebrafish). Expression analysis suggested independent regulation of the complementary Slc34a mRNAs. Analysis of randomly selected bi-directionally transcribed human/mouse loci revealed limited phylogenetic conservation and independent regulation of NATs. They were reduced on X chromosomes and clustered in regions that escape inactivation. Locus structure and expression pattern suggest a NATs-associated regulatory mechanisms in testis unrelated to the physiological role of the sense transcript encoded protein.

Keywords: Evolution; Human; Mouse; Na-phosphate transport; Natural antisense transcript.

Publication types

  • Comparative Study

MeSH terms

  • Alternative Splicing*
  • Animals
  • Cloning, Molecular / methods*
  • Databases, Genetic
  • Evolution, Molecular
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Kidney / metabolism
  • Male
  • Mice
  • Phylogeny
  • Profilins / genetics*
  • Profilins / metabolism*
  • Promoter Regions, Genetic
  • RNA, Antisense / genetics*
  • RNA, Antisense / metabolism
  • Sodium-Phosphate Cotransporter Proteins, Type IIa / antagonists & inhibitors*
  • Sodium-Phosphate Cotransporter Proteins, Type IIa / genetics
  • Testis / metabolism
  • Tissue Distribution


  • Profilins
  • RNA, Antisense
  • SLC34A1 protein, human
  • Sodium-Phosphate Cotransporter Proteins, Type IIa