A transcriptional switch controls meiosis

Abstract

A key protein involved in the segregation of meiotic chromosomes is produced 'just in time' by the regulated expression of two mRNA isoforms.

Keywords: S. cerevisiae; budding yeast; chromosomes; gene regulation; genes; kinetochore; meiosis; transcription; uORF translation.

Figure 1.. Transcriptional switching between two mRNA transcripts regulates the assembly of the kinetochore during meiosis.

(A) During prophase, homologous chromosomes undergo recombination to exchange genetic information (right). The kinetochore must be dismantled during this time so that chromosomes do not prematurely separate. Cells do this by limiting the availability of a subunit of the kinetochore called Ndc80 (left top). First, Ume6-Ime1 binds to an upstream promoter (thick black arrow) and the DNA is transcribed to produce an extended mRNA transcript named NDC80^luti. This process also results in the deposition of methylation marks (small blue circles) on histones (brown cyclinders). Enzymes called histone deacetylases (Set3 and Rpd3S) bind these marks and deacetylate the histones; the end result is to prevent the gene for Ndc80 (lilac rectangle) from being transcribed to produce a short mRNA transcript called NDC80^ORF. Reduced transcription from the NDC80^ORF promoter is indicated by the thinner black arrow. Additional regulation comes from upstream open reading frames (uORFs) in the extended transcript; the translation of these regions by the ribosome prevents translation reinitiation taking place at the NDC80 start codon (left bottom). (B) Following prophase, the kinetochore reassembles for chromosome segregation (right). Another transcription factor, Ndt80, binds the canonical NDC80 promoter (left top), and the DNA is transcribed to produce the shorter mRNA transcript. Translation of this transcript produces functional Ndc80 protein (left bottom), allowing the kinetochore to assemble and the chromosomes to segregate. Black arrows indicate direction of movement.