Regulation of spermatogenesis by testis-specific, cytoplasmic poly(A) polymerase TPAP

Science. 2002 Dec 6;298(5600):1999-2002. doi: 10.1126/science.1074632.

Abstract

Spermatogenesis is a highly specialized process of cellular differentiation to produce spermatozoa. This differentiation process accompanies morphological changes that are controlled by a number of genes expressed in a stage-specific manner during spermatogenesis. Here we show that in mice, the absence of a testis-specific, cytoplasmic polyadenylate [poly(A)] polymerase, TPAP, results in the arrest of spermiogenesis. TPAP-deficient mice display impaired expression of haploid-specific genes that are required for the morphogenesis of germ cells. The TPAP deficiency also causes incomplete elongation of poly(A) tails of particular transcription factor messenger RNAs. Although the overall cellular level of the transcription factor TAF10 is unaffected, TAF10 is insufficiently transported into the nucleus of germ cells. We propose that TPAP governs germ cell morphogenesis by modulating specific transcription factors at posttranscriptional and posttranslational levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle Proteins
  • Cytoplasm / enzymology
  • DNA-Binding Proteins
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Targeting
  • In Situ Nick-End Labeling
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Organ Size
  • Poly A / metabolism
  • Polynucleotide Adenylyltransferase / genetics
  • Polynucleotide Adenylyltransferase / metabolism*
  • Protein Biosynthesis
  • RNA, Messenger / metabolism*
  • Spermatids / physiology
  • Spermatocytes / physiology
  • Spermatogenesis*
  • Spermatozoa / physiology*
  • Testis / enzymology*
  • Testis / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • mRNA Cleavage and Polyadenylation Factors / genetics
  • mRNA Cleavage and Polyadenylation Factors / metabolism

Substances

  • Cell Cycle Proteins
  • Cpeb1 protein, mouse
  • DNA-Binding Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Sycp1 protein, mouse
  • Sycp3 protein, mouse
  • Transcription Factors
  • mRNA Cleavage and Polyadenylation Factors
  • Poly A
  • Polynucleotide Adenylyltransferase