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.
Highlights
Spermiogenesis is the process by which postmeiotic round spermatids (RSs) differentiate into elongated spermatids
In the present study, we demonstrated that Paip2a is required for late spermiogenesis through maintenance of Poly(A)-binding protein (Pabp) homeostasis
In Paip2a/Paip2b-DKO mice, the translation of mRNAs encoding proteins such as basic nuclear proteins needed for late spermiogenesis was dramatically reduced, which was associated with persistent expression and elevated activity of Pabp
Summary
Spermiogenesis is the process by which postmeiotic round spermatids (RSs) differentiate into elongated spermatids. Regulated protein expression of components in each step is essential for proper germ cell differentiation. While regulated gene expression is essential for germ cell development, transcription ceases at mid-spermiogenesis in RSs [2, 3]. MRNAs encoding proteins that are needed for late spermiogenesis are expressed in early spermatogenesis and stored as translationally repressed messenger ribonucleoprotein particles (mRNPs). These mRNAs are subsequently translated in elongating and elongated spermatids (ESs) [3,4,5], resulting in uncoupling between transcription and translation [2, 6,7,8]. Since the regulation of protein expression at specific steps of male germ cell development is essential for proper germ cell differentiation and male fertility, understanding the molecular basis of this regulation is central to understanding how male germ cells are produced
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