RNA Binding Protein Nanos2 Organizes Post-transcriptional Buffering System to Retain Primitive State of Mouse Spermatogonial Stem Cells.

Zhi Zhou, Takayuki Shirakawa, Kazuyuki Ohbo, Aiko Sada, Quan Wu, Kazuteru Hasegawa, Rie Saba, Yumiko Saga

Developmental cell 2015 Jul 6

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In many adult tissues, homeostasis relies on self-renewing stem cells that are primed for differentiation. The reconciliation mechanisms of these characteristics remain a fundamental question in stem cell biology. We propose that regulation at the post-transcriptional level is essential for homeostasis in murine spermatogonial stem cells (SSCs). Here, we show that Nanos2, an evolutionarily conserved RNA-binding protein, works with other cellular messenger ribonucleoprotein (mRNP) components to ensure the primitive status of SSCs through a dual mechanism that involves (1) direct recruitment and translational repression of genes that promote spermatogonial differentiation and (2) repression of the target of rapamycin complex 1 (mTORC1), a well-known negative pathway for SSC self-renewal, by sequestration of the core factor mTOR in mRNPs. This mechanism links mRNA turnover to mTORC1 signaling through Nanos2-containing mRNPs and establishes a post-transcriptional buffering system to facilitate SSC homeostasis in the fluctuating environment within the seminiferous tubule. Copyright © 2015 Elsevier Inc. All rights reserved.

Citation

Zhi Zhou, Takayuki Shirakawa, Kazuyuki Ohbo, Aiko Sada, Quan Wu, Kazuteru Hasegawa, Rie Saba, Yumiko Saga. RNA Binding Protein Nanos2 Organizes Post-transcriptional Buffering System to Retain Primitive State of Mouse Spermatogonial Stem Cells. Developmental cell. 2015 Jul 6;34(1):96-107