![]() The released RNA is not exported to the cytoplasm but polyadenylated by TRAMP and nucleolytically attacked by the exosome that trims snoRNAs to their mature length and fully degrades CUTs. One important feature of this pathway is its association with proteins involved in nuclear RNA degradation such as the exosome and its cofactor, the Trf4-Mtr4-Air (TRAMP) complex. Small nucleolar RNAs (snoRNAs) and cryptic unstable transcripts (CUTs), a prominent class of RNAPII pervasive transcripts, are typical targets of NNS-dependent termination. The second pathway depends on the NNS (Nrd1-Nab3-Sen1) complex and is responsible for terminating transcription of genes that do not code for proteins. If they contain premature stop codons, they are subject to the nonsense mediated decay and might not be detected in wild-type cells ( van Dijk et al., 2011 Malabat et al., 2015). Transcription terminated by this pathway produces RNAs that are exported to the cytoplasm and enter translation. Besides participating in the production of mRNAs, this pathway is also important for transcription termination of several classes of non-coding RNAs, namely SUTs (stable unannotated transcripts) and XUTs (Xrn1-dependent unstable transcripts) ( Marquardt et al., 2011). ![]() The first is employed for termination of mRNA coding genes and depends on the CPF-CF (cleavage and polyadenylation factor-cleavage factor) complex. In Saccharomyces cerevisiae cells, two main pathways are known for terminating normal and pervasive RNAPII transcription events ( Porrua et al., 2016). Transcription termination limits the extension of many non-coding transcription events, compensating, to some extent, the promiscuity of initiation (for recent reviews see: Jensen et al., 2013 Porrua and Libri, 2015). cerevisiae, pervasive transcription accounts for the production of a multitude of transcripts generally non-coding, many of which undergo degradation in the nucleus or the cytoplasm ( Jacquier, 2009 Porrua and Libri, 2015). The generalized presence of transcribing RNA polymerases, not necessarily associated to the production of stable RNAs, defines pervasive or hidden transcription, which is a conserved feature of both eukaryotic and prokaryotic transcriptomes. ![]() However, in the last decade, many genome-wide studies based on the direct detection of RNA polymerase II (RNAPII) have clearly established that transcription extends largely beyond the limits of regions annotated for coding functional RNA or protein products ( Jacquier, 2009 Porrua and Libri, 2015). The annotation of transcription units has traditionally heavily relied on the detection of RNA molecules. Overall, our results have important implications for understanding the impact of genomic location on origin function. ![]() We show that low, physiological levels of pervasive transcription impact the function of replication origins. We propose that quasi-symmetrical binding of the ORC complex to ARS borders and/or pre-RC formation are responsible for pausing and termination. 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 studied the relationships between pervasive transcription and replication origin activity using high-resolution transcription maps. The influence of transcription on ARSs function has been studied for decades, but these earlier studies have neglected the role of non-annotated transcription. In budding yeast, replication originates from Autonomously Replicating Sequences (ARSs), generally located in intergenic regions. RNA polymerase (RNAPII) transcription occurs pervasively, raising the important question of its functional impact on other DNA-associated processes, including replication.
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