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PAN2 maintains mRNA poly(A) tail homeostasis and regulates translation during spermiogenesis in mice

Xuan Wu1, Yu-Ke Wu1, Meng-Yan Jia1

  • 1Life Sciences Institute, Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.

Nature Communications
|February 19, 2026
PubMed

Insights

The PAN2 enzyme is crucial for male fertility, as its absence causes sperm development arrest. Loss of PAN2 disrupts mRNA poly(A) tail regulation, impacting translation efficiency and spermatid differentiation.

Area of Science:

  • Molecular Biology
  • Reproductive Biology
  • Genetics

Background:

  • Polyadenylation and deadenylation are key mRNA regulatory processes in eukaryotes.
  • PAN2-PAN3 and CCR4-NOT are major deadenylase complexes, but PAN2's in vivo role in mammals is unclear.

Purpose of the Study:

  • To investigate the in vivo function of the PAN2 enzyme in mammalian spermatogenesis.
  • To elucidate the molecular mechanisms underlying male infertility caused by Pan2 deficiency.

Main Methods:

  • Germline-specific deletion of Pan2 in mice.
  • PAIso-seq2 and mass spectrometry for poly(A) tail and proteomic analysis.
  • Ribo-lite and co-immunoprecipitation (IP-MS) to assess translation and protein interactions.

Main Results:

  • Pan2 deletion caused male infertility due to spermatogenic arrest at steps 8/9.
  • Disrupted stage-specific poly(A) tail remodeling and reduced translation efficiency in Pan2-null round spermatids.
  • PAN2 interacts with PABPC1 and translation initiation factors; their levels decrease upon Pan2 loss.

Conclusions:

  • PAN2 plays a critical physiological role in spermiogenesis.
  • PAN2 is essential for maintaining translational machinery stability and efficient mRNA processing during sperm development.

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