scholarly journals YTH-RNA-binding protein prevents deleterious expression of meiotic proteins by tethering their mRNAs to nuclear foci

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Yuichi Shichino ◽  
Yoko Otsubo ◽  
Yoshitaka Kimori ◽  
Masayuki Yamamoto ◽  
Akira Yamashita

Accurate and extensive regulation of meiotic gene expression is crucial to distinguish germ cells from somatic cells. In the fission yeast Schizosaccharomyces pombe, a YTH family RNA-binding protein, Mmi1, directs the nuclear exosome-mediated elimination of meiotic transcripts during vegetative proliferation. Mmi1 also induces the formation of facultative heterochromatin at a subset of its target genes. Here, we show that Mmi1 prevents the mistimed expression of meiotic proteins by tethering their mRNAs to the nuclear foci. Mmi1 interacts with itself with the assistance of a homolog of Enhancer of Rudimentary, Erh1. Mmi1 self-interaction is required for foci formation, target transcript elimination, their nuclear retention, and protein expression inhibition. We propose that nuclear foci formed by Mmi1 are not only the site of RNA degradation, but also of sequestration of meiotic transcripts from the translation machinery.

2011 ◽  
Vol 22 (16) ◽  
pp. 2875-2885 ◽  
Author(s):  
Mai Nguyen Chi ◽  
Jacques Auriol ◽  
Bernard Jégou ◽  
Dimitris L. Kontoyiannis ◽  
James M.A. Turner ◽  
...  

Posttranscriptional mechanisms are crucial to regulate spermatogenesis. Accurate protein synthesis during germ cell development relies on RNA binding proteins that control the storage, stability, and translation of mRNAs in a tightly and temporally regulated manner. Here, we focused on the RNA binding protein Embryonic Lethal Abnormal Vision (ELAV) L1/Human antigen R (HuR) known to be a key regulator of posttranscriptional regulation in somatic cells but the function of which during gametogenesis has never been investigated. In this study, we have used conditional loss- and gain-of-function approaches to address this issue in mice. We show that targeted deletion of HuR specifically in germ cells leads to male but not female sterility. Mutant males are azoospermic because of the extensive death of spermatocytes at meiotic divisions and failure of spermatid elongation. The latter defect is also observed upon HuR overexpression. To elucidate further the molecular mechanisms underlying spermatogenesis defects in HuR-deleted and -overexpressing testes, we undertook a target gene approach and discovered that heat shock protein (HSP)A2/HSP70-2, a crucial regulator of spermatogenesis, was down-regulated in both situations. HuR specifically binds hspa2 mRNA and controls its expression at the translational level in germ cells. Our study provides the first genetic evidence of HuR involvement during spermatogenesis and reveals Hspa2 as a target for HuR.


2011 ◽  
Vol 286 (43) ◽  
pp. 37063-37066 ◽  
Author(s):  
Philip J. Uren ◽  
Suzanne C. Burns ◽  
Jianhua Ruan ◽  
Kusum K. Singh ◽  
Andrew D. Smith ◽  
...  

2017 ◽  
Vol 37 (18) ◽  
Author(s):  
Jonathan Merran ◽  
Jeffry L. Corden

ABSTRACT Termination of Saccharomyces cerevisiae RNA polymerase II (Pol II) transcripts occurs through two alternative pathways. Termination of mRNAs is coupled to cleavage and polyadenylation while noncoding transcripts are terminated through the Nrd1-Nab3-Sen1 (NNS) pathway in a process that is linked to RNA degradation by the nuclear exosome. Some mRNA transcripts are also attenuated through premature termination directed by the NNS complex. In this paper we present the results of nuclear depletion of the NNS component Nab3. As expected, many noncoding RNAs fail to terminate properly. In addition, we observe that nitrogen catabolite-repressed genes are upregulated by Nab3 depletion.


1999 ◽  
pp. 343 ◽  
Author(s):  
Shozo Danno ◽  
Tadashi Matsuda ◽  
Hiroyuki Nishiyama ◽  
Hiromu Tokuchi ◽  
Osamu Yoshida ◽  
...  

2016 ◽  
Vol 6 (4) ◽  
pp. 1031-1047 ◽  
Author(s):  
Gabriela Huelgas-Morales ◽  
Carlos Giovanni Silva-García ◽  
Laura S. Salinas ◽  
David Greenstein ◽  
Rosa E. Navarro

2018 ◽  
Author(s):  
Yuichi Shichino ◽  
Yoko Otsubo ◽  
Yoshitaka Kimori ◽  
Masayuki Yamamoto ◽  
Akira Yamashita

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