Meiotic gene silencing complex MTREC/NURS recruits the nuclear exosome to YTH-RNA-binding protein Mmi1

Accurate target recognition in transcript degradation is crucial for regulation of gene expression. In the fission yeast Schizosaccharomyces pombe, a number of meiotic transcripts are recognized by a YTH-family RNA-binding protein, Mmi1, and selectively degraded by the nuclear exosome during mitotic growth. Mmi1 forms nuclear foci in mitotically growing cells, and the nuclear exosome colocalizes to such foci. However, it remains elusive how Mmi1 and the nuclear exosome are connected. Here, we show that a complex called MTREC (Mtl1-Red1 core) or NURS (nuclear RNA silencing) that consists of a zinc-finger protein, Red1, and an RNA helicase, Mtl1, is required for the recruitment of the nuclear exosome to Mmi1 foci. Physical interaction between Mmi1 and the nuclear exosome depends on Red1. Furthermore, a chimeric protein involving Mmi1 and Rrp6, which is a nuclear-specific component of the exosome, suppresses the ectopic expression phenotype of meiotic transcripts in red1 Delta cells and mtl1 mutant cells. These data indicate that the primary function of MTREC/NURS in meiotic transcript elimination is to link Mmi1 to the nuclear exosome physically. Author summary Since abnormal gene expression is detrimental to proliferation, cells possess a number of mechanisms to regulate gene expression at transcriptional and post-transcriptional levels. In particular, expression of meiotic genes is rigorously repressed in somatic cells because their aberrant expression causes severe cellular defects including genome instability and tumorigenesis. In the fission yeast Schizosaccharomyces pombe, selective degradation of meiotic transcripts is employed to prevent their deleterious expression during mitotic growth. Meiotic transcripts are recognized by a YTH-family RNA-binding protein, Mmi1. Mmi1 then induces their selective degradation by the nuclear exosome, which is a highly conserved exonuclease complex. However, little is known how Mmi1 cooperates with the nuclear exosome. Here, we demonstrate that the interaction of Mmi1 with the nuclear exosome is mediated by a complex termed MTREC/NURS that is composed of a conserved zinc-finger protein, Red1, and an RNA helicase, Mtl1. Our findings shed light on the target recognition mechanisms of post-transcriptional regulation.