Hexanucleotide motifs mediate recruitment of the RNA elimination machinery to silent meiotic genes.
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.
Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Hongo, Tokyo 113-0033, Japan. ymst@kazusa.or.jp
Akira
A
Yamashita
Yuichi
Y
Shichino
Hirotsugu
H
Tanaka
Edwige
E
Hiriart
Leila
L
Touat-Todeschini
Aurélia
A
Vavasseur
Da-Qiao
DQ
Ding
Yasushi
Y
Hiraoka
André
A
Verdel
Masayuki
M
Yamamoto
D001483:Base Sequence; D055354:Exosomes / Q000378:metabolism; D020868:Gene Silencing; D005800:Genes, Fungal; D008540:Meiosis / Q000235:genetics; D016296:Mutagenesis; D012331:RNA, Fungal / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism; D020080:Tandem Repeat Sequences; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics / Q000378:metabolism
C512176:Mmi1 protein, S pombe; D012331:RNA, Fungal; D029702:Schizosaccharomyces pombe Proteins; D039221:mRNA Cleavage and Polyadenylation Factors