The poly(A)-binding protein partner Paip2a controls translation during late spermiogenesis in mice
Akiko Yanagiya, Geraldine Delbes, Yuri V. Svitkin, Bernard Robaire, Nahum Sonenberg
Akiko Yanagiya, Geraldine Delbes, Yuri V. Svitkin, Bernard Robaire, Nahum Sonenberg
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Research Article

The poly(A)-binding protein partner Paip2a controls translation during late spermiogenesis in mice

Abstract

Translational control plays a key role in late spermiogenesis. A number of mRNAs encoding proteins required for late spermiogenesis are expressed in early spermatids but are stored as translationally inactive messenger ribonucleoprotein particles (mRNPs). The translation of these mRNAs is associated with shortening of their poly(A) tail in late spermiogenesis. Poly(A)-binding protein (Pabp) plays an important role in mRNA stabilization and translation. Three Pabp-interacting proteins, Paip1, Paip2a, and Paip2b, have been described. Paip2a is expressed in late spermatids. To investigate the role of Paip2 in spermiogenesis, we generated mice with knockout of either Paip2a or Paip2b and double-KO (DKO) mice lacking both Paip2a and Paip2b. Paip2a-KO and Paip2a/Paip2b-DKO mice exhibited male infertility. Translation of several mRNAs encoding proteins essential to male germ cell development was inhibited in late spermiogenesis in Paip2a/Paip2b-DKO mice, resulting in defective elongated spermatids. Inhibition of translation in Paip2a/Paip2b-DKO mice was caused by aberrant increased expression of Pabp, which impaired the interaction between eukaryotic initiation factor 4E (eIF4E) and the cap structure at the 5′ end of the mRNA. We therefore propose a model whereby efficient mRNA translation in late spermiogenesis occurs at an optimal concentration of Pabp, a condition not fulfilled in Paip2a/Paip2b-DKO mice.

Authors

Akiko Yanagiya, Geraldine Delbes, Yuri V. Svitkin, Bernard Robaire, Nahum Sonenberg

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Figure 3

Phenotypes of Paip2a/Paip2b-KO mice.

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Phenotypes of Paip2a/Paip2b-KO mice. (A) Body weights of WT and Paip...
(A) Body weights of WT and Paip2a/Paip2b-DKO mice. Values are mean ± SEM of 20–23 mice at 10–12 weeks old. *P < 0.05 using an unpaired t test. (B) Reproductive organ weights of WT and Paip2a/Paip2b-DKO mice. Organ weights per body weight (BW) are shown. Values are mean ± SEM of 10–16 mice for testis and epididymis and 8–14 mice for seminal vesicle and prostate. *P < 0.05 using an unpaired t test. (C) Sperm count in testes, caput/corpus epididymides, and cauda epididymides of WT and Paip2a/Paip2b-DKO mice. Values are mean ± SEM of 5 mice. *P < 0.05 using an unpaired t test. (D and E) Histology of testes (D) and caput and cauda epididymides (E) from WT and Paip2a/Paip2b-DKO mice by H&E staining. Arrows indicate elongating spermatids; arrowheads in WT mice indicate mature sperm released from the epithelium at stage VII; and arrowheads in Paip2a/Paip2b-DKO mice show sperm that could not be released into the lumen in later stages (D). The asterisks indicate mature sperm in the lumen of WT epididymis (E). Scale bars: 25 μm.