Journal Article

The RNAPII-CTD Maintains Genome Integrity through Inhibition of Retrotransposon Gene Expression and Transposition

Aristizabal, Maria J., Negri, Gian Luca, Kobor, Michael S.

2015

Overview

RNA polymerase II (RNAPII) contains a unique C-terminal domain that is composed of heptapeptide repeats and which plays important regulatory roles during gene expression. RNAPII is responsible for the transcription of most protein-coding genes, a subset of non-coding genes, and retrotransposons. Retrotransposon transcription is the first step in their multiplication cycle, given that the RNA intermediate is required for the synthesis of cDNA, the material that is ultimately incorporated into a new genomic location. Retrotransposition can have grave consequences to genome integrity, as integration events can change the gene expression landscape or lead to alteration or loss of genetic information. Given that RNAPII transcribes retrotransposons, we sought to investigate if the RNAPII-CTD played a role in the regulation of retrotransposon gene expression. Importantly, we found that the RNAPII-CTD functioned to maintaining genome integrity through inhibition of retrotransposon gene expression, as reducing CTD length significantly increased expression and transposition rates of Ty1 elements. Mechanistically, the increased Ty1 mRNA levels in the rpb1-CTD11 mutant were partly due to Cdk8-dependent alterations to the RNAPII-CTD phosphorylation status. In addition, Cdk8 alone contributed to Ty1 gene expression regulation by altering the occupancy of the gene-specific transcription factor Ste12. Loss of STE12 and TEC1 suppressed growth phenotypes of the RNAPII-CTD truncation mutant. Collectively, our results implicate Ste12 and Tec1 as general and important contributors to the Cdk8, RNAPII-CTD regulatory circuitry as it relates to the maintenance of genome integrity.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Alleles / Analysis / Cyclin-Dependent Kinase 8 - genetics / Cyclin-Dependent Kinase 8 - metabolism / Defects / DNA, Complementary - biosynthesis / DNA, Complementary - genetics / DNA-Binding Proteins - biosynthesis / DNA-Binding Proteins - genetics / Enzymes / Gene expression / Gene Expression Regulation, Fungal / Gene mutations / Genome / Genomes / Kinases / Mutation / Phenotype / Phosphorylation / Protein Structure, Tertiary / Proteins / Retroelements - genetics / RNA polymerase / RNA Polymerase II - genetics / RNA Polymerase II - metabolism / RNA polymerases / RNA-Binding Proteins - genetics / Roles / Saccharomyces cerevisiae / Saccharomyces cerevisiae Proteins - biosynthesis / Saccharomyces cerevisiae Proteins - genetics / Saccharomyces cerevisiae Proteins - metabolism / Studies / Transcription factors / Transcription Factors - biosynthesis / Transcription Factors - genetics / Transcription, Genetic