Interaction between microRNAs and actin-associated protein Arpc5 regulates translational suppression during male germ cell differentiation

Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5750-5. doi: 10.1073/pnas.1117837109. Epub 2012 Mar 23.

Abstract

Decoupling of transcription and translation during postmeiotic germ cell differentiation is critical for successful spermatogenesis. Here we establish that the interaction between microRNAs and actin-associated protein Arpc5 sets the stage for an elaborate translational control mechanism by facilitating the sequestration of germ cell mRNAs into translationally inert ribonucleoprotein particles until they are later translated. Our studies reveal that loss of microRNA-dependent regulation of Arpc5, which controls the distribution of germ cell mRNAs between translationally active and inactive pools, results in abnormal round spermatid differentiation and impaired fertility. Interestingly, Arpc5 functions as a broadly acting translational suppressor, as it inhibits translation initiation by blocking 80S formation and facilitates the transport of mRNAs to chromatoid/P bodies. These findings identify a unique role for actin-associated proteins in translational regulation, and suggest that mRNA-specific and general translational control mechanisms work in tandem to regulate critical germ cell differentiation events and diverse somatic cell functions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Actin-Related Protein 2-3 Complex / metabolism*
  • Animals
  • Base Sequence
  • Cell Differentiation / genetics*
  • Chromatin / metabolism
  • Enzyme Activation
  • Gene Expression Regulation
  • Haploidy
  • HeLa Cells
  • Humans
  • Male
  • Meiosis / genetics
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Protamines / metabolism
  • Protein Binding
  • Protein Biosynthesis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reproduction
  • Ribonuclease III / metabolism
  • Ribosomes / metabolism
  • Sperm Head / metabolism
  • Sperm Head / pathology
  • Sperm Head / ultrastructure
  • Spermatozoa / metabolism*
  • Spermatozoa / pathology*
  • Testis / abnormalities
  • Testis / pathology
  • Testis / ultrastructure

Substances

  • Actin-Related Protein 2-3 Complex
  • Arpc5 protein, mouse
  • Chromatin
  • MicroRNAs
  • Protamines
  • RNA, Messenger
  • Ribonuclease III