RNA decay, evolution, and the testis

RNA Biol. 2017 Feb;14(2):146-155. doi: 10.1080/15476286.2016.1265199. Epub 2016 Dec 2.


NMD is a highly conserved pathway that degrades specific subsets of RNAs. There is increasing evidence for roles of NMD in development. In this commentary, we focus on spermatogenesis, a process dramatically impeded upon loss or disruption of NMD. NMD requires strict regulation for normal spermatogenesis, as loss of a newly discovered NMD repressor, UPF3A, also causes spermatogenic defects, most prominently during meiosis. We discuss the unusual evolution of UPF3A, whose paralog, UPF3B, has the opposite biochemical function and acts in brain development. We also discuss the regulation of NMD during germ cell development, including in chromatoid bodies, which are specifically found in haploid germ cells. The ability of NMD to coordinately degrade batteries of RNAs in a regulated fashion during development is akin to the action of transcriptional pathways, yet has the advantage of driving rapid changes in gene expression.

Keywords: NMD; RNA decay; neofunctionalization; spermatogenesis; subfunctionalization.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Evolution*
  • Cell Differentiation / genetics
  • Gene Expression Regulation*
  • Germ Cells / cytology
  • Germ Cells / metabolism
  • Humans
  • Male
  • Nonsense Mediated mRNA Decay
  • Protein Binding
  • RNA Stability*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Spermatogenesis / genetics*
  • Substrate Specificity
  • Testis / physiology*


  • RNA, Messenger
  • RNA-Binding Proteins
  • Repressor Proteins
  • UPF3A protein, human