scholarly journals Structural basis for the specific recognition of DSR by the YTH domain containing protein Mmi1

2017 ◽  
Author(s):  
Baixing Wu ◽  
Jinhao Xu ◽  
Shichen Su ◽  
Hehua Liu ◽  
Jianhua Gan ◽  
...  

AbstractMeiosis is one of the most dramatic differentiation programs accompanied by a striking change in gene expression profiles, whereas a number of meiosis-specific transcripts are expressed untimely in mitotic cells. The entry of meiosis will be blocked as the accumulation of meiosis-specific mRNAs during the mitotic cell in fission yeast Schizosaccharomyces pombe. A YTH domain containing protein Mmi1 was identified as a pivotal effector in a post-transcriptional event termed selective elimination of meiosis-specific mRNAs, Mmi1 can recognize and bind a class of meiosis-specific transcripts expressed inappropriately in mitotic cells, which contain a conservative motif called DSR as a mark to remove them in cooperation with nuclear exosomes. Here we report the 1.6 Å resolution crystal structure of the YTH domain of Mmi1 binds to high-affinity RNA targets r(A1U2U3A4A5A6C7A8) containing DSR core motif. Our structure observations, supported by site-directed mutations of key residues illustrate the mechanism for specific recognition of DSR-RNA by Mmi1. Moreover, different from other YTH domain family proteins, Mmi1 YTH domain has a distinctive function although it has a similar fold as other ones.

Open Biology ◽  
2012 ◽  
Vol 2 (3) ◽  
pp. 120014 ◽  
Author(s):  
Akira Yamashita ◽  
Yuichi Shichino ◽  
Hirotsugu Tanaka ◽  
Edwige Hiriart ◽  
Leila Touat-Todeschini ◽  
...  

The selective elimination system blocks the accumulation of meiosis-specific mRNAs during the mitotic cell cycle in fission yeast. These mRNAs harbour a region, the determinant of selective removal (DSR), which is recognized by a YTH-family RNA-binding protein, Mmi1. Mmi1 directs target transcripts to destruction in association with nuclear exosomes. Hence, the interaction between DSR and Mmi1 is crucial to discriminate mitosis from meiosis. Here, we show that Mmi1 interacts with repeats of the hexanucleotide U(U/C)AAAC that are enriched in the DSR. Disruption of this ‘DSR core motif’ in a target mRNA inhibits its elimination. Tandem repeats of the motif can function as an artificial DSR. Mmi1 binds to it in vitro . Thus, a core motif cluster is responsible for the DSR activity. Furthermore, certain variant hexanucleotide motifs can augment the function of the DSR core motif. Notably, meiRNA, which composes the nuclear Mei2 dot required to suppress Mmi1 activity during meiosis, carries numerous copies of the core/augmenting motifs on its tail and is indeed degraded by the Mmi1/exosome system, indicating its likely role as decoy bait for Mmi1.


2004 ◽  
Vol 171 (4S) ◽  
pp. 349-350
Author(s):  
Gaelle Fromont ◽  
Michel Vidaud ◽  
Alain Latil ◽  
Guy Vallancien ◽  
Pierre Validire ◽  
...  

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