Abstract
Pervasive transcription is a widespread phenomenon leading to the production of a plethora of non‐coding RNAs (ncRNAs) without apparent function. Pervasive transcription poses a threat to proper gene expression that needs to be controlled. In yeast, the highly conserved helicase Sen1 restricts pervasive transcription by inducing termination of non‐coding transcription. However, the mechanisms underlying the specific function of Sen1 at ncRNAs are poorly understood. Here, we identify a motif in an intrinsically disordered region of Sen1 that mimics the phosphorylated carboxy‐terminal domain (CTD) of RNA polymerase II, and structurally characterize its recognition by the CTD‐interacting domain of Nrd1, an RNA‐binding protein that binds specific sequences in ncRNAs. In addition, we show that Sen1‐dependent termination strictly requires CTD recognition by the N‐terminal domain of Sen1. We provide evidence that the Sen1‐CTD interaction does not promote initial Sen1 recruitment, but rather enhances Sen1 capacity to induce the release of paused RNAPII from the DNA. Our results shed light on the network of protein–protein interactions that control termination of non‐coding transcription by Sen1.
Highlights
The concept of pervasive transcription emerged over a decade ago upon the discovery that a large fraction of both the prokaryotic and the eukaryotic transcriptomes is composed of non-coding RNAs without any obvious function
In a previous report (Tudek et al, 2014), we showed that Nrd1 CTD interaction domain (CID) domain can recognize a short sequence in Trf4 that mimic the S5PCTD of RNA polymerase II (RNAPII) and that we dubbed NIM for Nrd1-Interaction Motif
The S5P-carboxy-terminal domain (CTD) and Trf4 NIM share three important features: (i) they contain one or several negatively charged aa at the N-terminal portion that interact with a positively charged surface of the CID; (ii) they contain a Y residue followed by several aa at the C-terminal part that adopt a b-turn conformation and interact with a hydrophobic pocket of the CID; and (iii) they are placed in protein regions that are predicted to be intrinsically disordered and are fully accessible for the interaction with the CID
Summary
The concept of pervasive transcription emerged over a decade ago upon the discovery that a large fraction of both the prokaryotic and the eukaryotic transcriptomes is composed of non-coding RNAs (ncRNAs) without any obvious function. Pervasive transcription is potentially harmful for cell homeostasis since it can interfere with normal transcription of canonical genes and provoke the accumulation of toxic RNAs. all organisms studied to date have evolved different mechanisms to circumvent the negative consequences of pervasive transcription. All organisms studied to date have evolved different mechanisms to circumvent the negative consequences of pervasive transcription These mechanisms often rely on transcription termination and RNA degradation (for review, see Jensen et al, 2013). A pathway that depends on a macromolecular complex including the cleavage and polyadenylation factor (CPF) is essentially responsible for transcription termination at protein-coding genes, whereas the Nrd1-Nab3-Sen (NNS) complex targets a large fraction of the noncoding RNAs (ncRNAs) produced in the cell. While snoRNAs are important for the correct modification of rRNA, CUTs are generally considered as non-functional molecules (Wyers et al, 2005; Arigo et al, 2006; Thiebaut et al, 2006; Schulz et al, 2013)
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