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 6

Translation inhibition in late spermiogenesis of Paip2a/Paip2b-DKO mice.

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Translation inhibition in late spermiogenesis of Paip2a/Paip2b-DKO mice....
(A) Levels of basic nuclear proteins (Prm1, Tp1, Tp2, and histone H1) from testes of WT and Paip2a/Paip2b-DKO mice were analyzed by acid-urea polyacrylamide gel electrophoresis. (B) Tp2 expression in testes at stages X–XII from WT and Paip2a/Paip2b-DKO mice analyzed by immunohistochemistry. Arrows indicate Tp2-positive spermatids, and arrowheads indicate Tp2-negative spermatids. Scale bar: 10 μm. (C) Expression of Paip2a, Paip2b, Pabpc1, and Pabpc2 in PSs, RSs, and ESs of WT (lanes 1–3) and Paip2a/Paip2b-DKO (lanes 4–6) mice analyzed by Western blotting. (D) Prm1 mRNA in testes from WT, Paip2a-KO, Paip2b-KO, and Paip2a/Paip2b-DKO mice analyzed by Northern blot analysis. Numbers on the right denote nucleotides, and arrows indicate ladder RNA fragments. (E) Ladder RNA fragments were generated by cleavage of poly(A) tail. Total testis RNA of WT and Paip2a/Paip2b-DKO mice was incubated without (–) or with (+) oligo(dT) and then treated with RNase H, followed by Northern blot analysis. Ribosomal 18S RNA (1,870 nucleotides) was used as a control for the absence of nonspecific RNA degradation during this experiment.