Too much PABP, too little translation
Hemant K. Kini, … , Melanie R. Vishnu, Stephen A. Liebhaber
Hemant K. Kini, … , Melanie R. Vishnu, Stephen A. Liebhaber
Published August 25, 2010
Citation Information: J Clin Invest. 2010;120(9):3090-3093. https://doi.org/10.1172/JCI44091.
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Commentary

Too much PABP, too little translation

Abstract

Posttranscriptional regulation is of critical importance during mammalian spermiogenesis. A set of mRNAs that encode proteins critical to normal sperm formation are synthesized early in the process of male germ cell differentiation and are stored in a repressed state. These mRNAs are subsequently translationally activated during the process of spermatid elongation and maturation. Of note, the translationally repressed mRNAs contain long poly(A) tails that are dramatically shortened during the translational activation process. Understanding the mechanisms that underlie this process of mRNA storage and subsequent translational activation has been a long-standing goal. The relationship of the poly(A) tail to translational control is intimately related to the functions of the cognate poly(A)-binding proteins (PABPs). In this issue of the JCI, Yanagiya and colleagues use a set of knockout mice to demonstrate a novel functional role for a particular modulator of PABP function, PABP-interacting protein 2a (PAIP2A), in the normal terminal differentiation of male germ cells.

Authors

Hemant K. Kini, Melanie R. Vishnu, Stephen A. Liebhaber

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Figure 2

Male germ cell–specific translational initiation/activation.

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Male germ cell–specific translational initiation/activation. mRNAs gener...
mRNAs generated early in spermatogenesis are stored with long poly(A) tails (A). Their subsequent activation during the terminal phases of sperm differentiation is associated with shortening of the poly(A) tail (B) and translational activation (C). The underlying mechanisms of activation remain unclear, and the question of whether the poly(A) shortening plays an active role in this process remains unanswered. The study by Yanagiya et al. (10) demonstrates that this pathway is in some way critically dependent on the presence of Paip2a. They propose that the knockout of Paip2a results in a pathologic retention of high levels of PABP in the late stages of spermatogenesis (D). In Paip2a-KO mice (10), the abundant PABP may interfere with normal interactions of poly(A)-bound PABP with the eIF4G by direct competition and/or by nonspecific coating of the mRNA, with consequent alterations in overall mRNA structure. The role of Paip2a in controlling PABP levels and/or its more specific role(s) in the translational activation pathway remain undefined.