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Transcriptional repression of CDC6 and SLD2 during meiosis is associated with production of short heterogeneous RNA isoforms

Author:
Phizicky, David V., Bell, Stephen P.
Source:
Chromosoma 2018 v.127 no.4 pp. 515-527
ISSN:
0009-5915
Subject:
DNA replication, chromosome segregation, gene expression regulation, genes, meiosis, messenger RNA, mitosis, open reading frames, ploidy, transcription initiation, yeasts
Abstract:
Execution of the meiotic and mitotic cell division programs requires distinct gene expression patterns. Unlike mitotic cells, meiotic cells reduce ploidy by following one round of DNA replication with two rounds of chromosome segregation (meiosis I and meiosis II). However, the mechanisms by which cells prevent DNA replication between meiosis I and meiosis II are not fully understood. Here, we show that transcriptional repression of two essential DNA replication genes, CDC6 and SLD2, is associated with production of shorter meiosis-specific RNAs containing the 3′ end of both genes. Despite the short CDC6 RNA coding for a short protein (Cdc6ˢʰᵒʳᵗ), this protein is not essential for meiosis and it does not have either a positive or negative impact on DNA replication. Production of CDC6ˢʰᵒʳᵗ mRNA does not require the upstream CDC6 promoter (PCDC₆) and is not a processed form of the full-length RNA. Instead, CDC6ˢʰᵒʳᵗ depends on transcription initiation from within the ORF upon repression of PCDC₆. Finally, using CDC6 genes from related yeast, we show that repression of full-length CDC6 mRNA is evolutionarily conserved and that this repression is consistently associated with production of unique short CDC6 RNAs. Together, these data demonstrate that meiotic cells transcriptionally repress full-length CDC6 and SLD2, and that inactivation of PCDC₆ results in heterogeneous transcription initiation from within the CDC6 ORF.
Agid:
6194946