Pervasive Transcription Fine-tunes Replication Origin Activity

Abstract

RNA polymerase (RNAPII) transcription occurs pervasively, which raises the important question of its functional impact on other DNA-associated processes, including replication. In budding yeast, replication originates from Autonomously Replicating Sequences (ARSs), generally located in intergenic regions. The influence of transcription on ARSs function has been studied for decades, but these earlier studies have necessarily neglected the role of non-annotated transcription. We studied the relationships between pervasive transcription and replication origin activity using high-resolution transcription maps. We show that ARSs alter the pervasive transcription landscape by pausing and terminating neighboring RNAPII transcription, thus limiting the occurrence of pervasive transcription within origins. We provide evidence that quasi-symmetrical binding of the ORC complex to ARS borders is responsible for pausing/termination. We also show that low, physiological levels of pervasive transcription impact the function of replication origins. Overall, our results have important implications for understanding the impact of genomic location on origin function.

Noncoding transcription influences the replication initiation program through chromatin regulation

“…3). Similar data were described in a recent paper (Candelli et al 2018). These observations indicate that nascent transcription influences ARS activity only beyond a certain threshold and that other parameters contribute to origin function.…”

The S. cerevisiae m6A-reader Pho92 impacts meiotic recombination by controlling key methylated transcripts

“…CRAC datasets were analyzed as previously described (Candelli et al, 2018) except for the normalization step. Briefly, data preprocessing steps include the 5’ adapter trimming, PCR duplicates and poly-A stretch removal and the reverse complement of the reads.…”

The prevention and resolution of DNA replication–transcription conflicts in eukaryotic cells

“…These elements often possess the features of enhancers or promoters, enforcing the notion that replication and transcription are coupled. In addition, numerous lines of evidence indicate that transcriptional initiation activity defines those replication origins that will fire efficiently (Candelli et al 2018;Chen et al 2019;Sequeira-Mendes et al 2009). This, in turn, enables replication and transcription to occur in a co-directional fashion.…”