Selective elimination of messenger RNA prevents an incidence of untimely meiosis

Abstract

Much remains unknown about the molecular regulation of meiosis. Here we show that meiosis-specific transcripts are selectively removed if expressed during vegetative growth in fission yeast. These messenger RNAs contain a cis-acting region--which we call the DSR--that confers this removal via binding to a YTH-family protein Mmi1. Loss of Mmi1 function severely impairs cell growth owing to the untimely expression of meiotic transcripts. Microarray analysis reveals that at least a dozen such meiosis-specific transcripts are eliminated by the DSR-Mmi1 system. Mmi1 remains in the form of multiple nuclear foci during vegetative growth. At meiotic prophase these foci precipitate to a single focus, which coincides with the dot formed by the master meiosis-regulator Mei2. A meiotic arrest due to the loss of the Mei2 dot is released by a reduction in Mmi1 activity. We propose that Mei2 turns off the DSR-Mmi1 system by sequestering Mmi1 to the dot and thereby secures stable expression of meiosis-specific transcripts.

Untimely expression of gametogenic genes in vegetative cells causes uniparental disomy

“…The following arrays, gene fusions and mutant alleles were previously described: lacO at pericentromeric regions lys1 and cen2-D107 and lacI-GFP at his7 loci 32 , tetO at cen2 and tetR-Tomato adjacent to zfs1 (Z locus) 27 , Padh1-rec8 + -3HA and Padh1-rec8 + -GFP 25 , mei4∆C<NAT 4 , and rec12 ∆ 33 . Deletion of mmi1 was performed in cells carrying a previously described truncated non-functional mei4 ( mei4∆C<NAT ) allele 4 to alleviate growth defects caused by derepression of mei4 in mitotic cells 15 .…”

“…The mmi1 ∆ strain carries a previously described truncated non-functional allele of mei4 4 , required to rescue the lethality observed upon the loss of Mmi1 15 . For each mutant, the set of genes enriched greater than two-fold was compared to previously annotated meiotic genes (a).…”

“…The YTH-family protein Mmi1 promotes degradation of meiotic gene transcripts by RNAi and the nuclear exosome 10,11,15–18 . Comparing the expression profiles of cells lacking RNAi components or Mmi1 revealed that a majority of the meiotic genes that were upregulated in ago1 ∆ or dcr1 ∆ RNAi mutants (85 out of 152) were also upregulated in mmi1 ∆ (Fig.…”

Cdk3, a conjugation-specific cyclin-dependent kinase, is essential for the initiation of meiosis in Tetrahymena thermophila

“…Here, responding to nutritional cues, Mei2 promotes exit from the mitotic cell cycle by antagonizing the elimination of meiotic mRNAs. [8][9][10][11] Thus, while the mechanisms of meiosis initiation are very different and the genes involved in these processes have little sequence homology, Cdks and cyclins play important roles in both S. cerevisiae and S. pombe.…”

Meiosis 2007 – Where have we got to and where are we going?

“…Remarkably, these transcripts harbour molecular tags Y the so-called DSRs (determinant of selective removal) that render them susceptible to removal by the RNAbinding protein Mmi1. Inactivation of the DSRMmi1 system is a key step in the mitosis Y meiosis switch and is mediated by Mei2 (Harigaya et al 2006). In conditions where meiosis is triggered, e.g following nutrient starvation, expression of Mei2 is stimulated, and the resulting Mei2 protein sequesters Mmi1 at a discrete Fdot_ in the meiotic nucleus where it can no longer orchestrate the elimination of meiotic transcripts.…”