The poly(A)-binding protein partner Paip2a controls translation during late spermiogenesis in mice
Akiko Yanagiya, … , Bernard Robaire, Nahum Sonenberg
Akiko Yanagiya, … , Bernard Robaire, Nahum Sonenberg
Published August 25, 2010
Citation Information: J Clin Invest. 2010;120(9):3389-3400. https://doi.org/10.1172/JCI43350.
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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 2

Generation of Paip2a/Paip2b-KO mouse.

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Generation of Paip2a/Paip2b-KO mouse. (A) Targeted disruption of Pai...
(A) Targeted disruption of Paip2a. Exons 2, 3, and 4 are depicted as filled boxes. The targeting regions are shown as bold lines. Filled arrows indicate 5′ probe and 3′ probe for Southern blot analysis. Open arrows indicate LoxP sites. Gray arrows indicate primers for genotyping (P1, P2, P3, and P4). (B) Targeted disruption of Paip2b. Exons 3 and 4 are shown as filled boxes. Gray arrows indicate primers for genotyping (P5, P6, P7, and P8). (C) Southern blot analysis of WT, Paip2a heterozygote, Paip2a-KO, Paip2b heterozygote, and Paip2b-KO mice probed by 5′ probes (see also Supplemental Figure 1). (D) Genotyping of WT, Paip2a-KO, Paip2b-KO, and Paip2a/Paip2b-DKO mice. Primer sets of P1 and P2, P3 and P4, and P1 and P4 were used to detect the first and second LoxP sites and the recombined loxP site of Paip2a, respectively. Primer sets of P5 and P6, P7 and P8, and P5 and P8 were used to detect the first LoxP site, the second LoxP site, and the recombined loxP site of Paip2b, respectively. (E) Western blot analysis of Paip2a, Paip2b, and Pabp in testes. (F) Western blot analysis of Paip2a, Paip2b, and Pabp in epididymides.