Sen1 has unique structural features grafted on the architecture of the Upf1‐like helicase family

Leonaitė, Bronislava; Han, Zhong Chao; Basquin, J.; Bonneau, Fabien; Libri, Domenico; Porrúa, Odil; Conti, Elena

doi:10.15252/embj.201696174

Cited by 45 publications

(76 citation statements)

References 61 publications

(120 reference statements)

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“…To further explore this interaction and its biological function, we mapped the interaction sites both in the replisome and Sen1. Sen1 contains an extended N-terminal domain and an essential and conserved helicase domain (Leonait _ e et al, 2017). To identify a region of Sen1 that is sufficient for binding replisomes, we generated TAP-tagged constructs of Sen1, expressed under an inducible GAL1 promoter ( Figure 1B).…”

Section: Sen1 Interacts With the Replisome Via Its N-terminal Domainmentioning

confidence: 99%

“…Sen1 is an Upf1-like helicase that plays a key role in transcription termination (Jankowsky, 2011;Steinmetz et al, 2006;Ursic et al, 1997;Porrua and Libri, 2013). Sen1 binds to the free 5 0 ends of either RNA or DNA substrates and unwind both double-stranded DNA (dsDNA) and DNA:RNA hybrids Leonait _ e et al, 2017;Martin-Tumasz and Brow, 2015;Porrua and Libri, 2013). In vitro analysis shows that Sen1 has high activity but limited processivity on DNA:RNA hybrid substrates .…”

Section: Introductionmentioning

confidence: 99%

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Sen1 Is Recruited to Replication Forks via Ctf4 and Mrc1 and Promotes Genome Stability

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Section: Sen1 Interacts With the Replisome Via Its N-terminal Domainmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sen1 Is Recruited to Replication Forks via Ctf4 and Mrc1 and Promotes Genome Stability

et al. 2020

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“…In this study, we identify and characterize the key interactions involved in Sen1 function. Sen1 is composed of a central helicase domain [amino acids (aa) 1,095–1,876] that is sufficient for transcription termination in vitro (Han et al , ; Leonait≐ et al , ), together with a large N‐terminal domain (aa 1–975) and a C‐terminal intrinsically disordered region (1,930–2,231). Here, we show that the C‐terminal end of Sen1 contains a short motif that mimics the phosphorylated CTD and is recognized by Nrd1 CID.…”

Section: Introductionmentioning

confidence: 99%

Termination of non‐coding transcription in yeast relies on both an RNA Pol II CTD interaction domain and a CTD‐mimicking region in Sen1

et al. 2020

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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.

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“…22 Leonaitė et al, 2017;Porrua and Libri, 2013). Neither in vitro nor in vivo Sen1 exhibits any 23 sequence-specific RNA-binding capability (Creamer et al, 2011;Porrua and Libri, 2013);…”

mentioning

confidence: 99%

“…Sen1 is 18 a highly conserved RNA and DNA helicase belonging to the superfamily 1 of helicases (Han 19 et al, 2017; Martin-Tumasz and Brow, 2015). Transcription termination by Sen1 involves its 20 translocation along the nascent RNA towards RNAPII and possibly subsequent contacts 21 between specific regions of Sen1 helicase domain and the polymerase (Han et al, 2017;22 Leonaitė et al, 2017;Porrua and Libri, 2013). Neither in vitro nor in vivo Sen1 exhibits any 23 sequence-specific RNA-binding capability (Creamer et al, 2011;Porrua and Libri, 2013);…”

mentioning

confidence: 99%

Termination of non-coding transcription in yeast relies on both a CTD-interaction domain and a CTD-mimic in Sen1

Han

Jasnovidova

Haidara

et al. 2018

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1Pervasive transcription is a widespread phenomenon leading to the production of a plethora 2 of non-coding RNAs (ncRNAs) without apparent function. Pervasive transcription poses a risk 3 that needs to be controlled to prevent the perturbation of gene expression. In yeast, the highly 4 conserved helicase Sen1 restricts pervasive transcription by inducing termination of non-5 coding transcription. However, the mechanisms underlying the specific function of Sen1 at 6 ncRNAs are poorly understood. Here we identify a motif in an intrinsically disordered region of 7 Sen1 that mimics the phosphorylated carboxy terminal domain (CTD) of RNA polymerase II 8 and characterize structurally its recognition by the CTD-interacting domain of Nrd1, an RNA-9 binding protein that binds specific sequences in ncRNAs. In addition, we show that Sen1-10 dependent termination strictly requires the recognition of the Ser5-phosphorylated form of the 11 CTD by the N-terminal domain of Sen1. Furthermore, we find that the N-terminal and the C-12 terminal domains of Sen1 can mediate intra-molecular interactions. Our results shed light onto 13 the network of protein-protein interactions that control termination of non-coding transcription 14 by Sen1. 16The concept of pervasive transcription emerged over a decade ago upon the discovery that a 2 large fraction of both the prokaryotic and the eukaryotic transcriptomes is composed of non-3 coding RNAs (ncRNAs) without any obvious function. Pervasive transcription is potentially 4 harmful for cell homeostasis since it can interfere with normal transcription of canonical genes 5 and provoke the accumulation of toxic RNAs. Therefore, all organisms studied to date have 6 evolved different mechanisms to circumvent the negative consequences of pervasive 7 transcription. These mechanisms often rely on transcription termination and RNA degradation 8 (for review, see Jensen et al., 2013). 9In S. cerevisiae there are two major pathways for termination of RNA polymerase II (RNAPII) 10 transcription. A pathway that depends on a macromolecular complex including the cleavage 11 and polyadenylation factor (CPF) is essentially responsible for transcription termination at 12 protein-coding genes, whereas the Nrd1-Nab3-Sen1 (NNS) complex targets a large fraction of 13 the non-coding RNAs (ncRNAs) produced in the cell. Specifically, the NNS complex terminates 14 transcription of most snoRNAs and a class of ncRNAs dubbed CUTs, for cryptic unstable 15 transcripts, that constitutes the major product of pervasive transcription (for review, see Porrua 16and Libri, 2015). While snoRNAs are important for the correct modification of rRNA, CUTs are 17 generally considered as non-functional molecules (Arigo et al., 2006;Schulz et al., 2013; 18 Thiebaut et al., 2006;Wyers et al., 2005). 19Each pathway is associated with distinct nuclease and polyA-polymerase activities that 20 determine the stability and functionality of the RNAs they take care of. Precursors of mRNAs 21 are cleaved at their 3' ends at the so-called polyA si...

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Sen1 has unique structural features grafted on the architecture of the Upf1‐like helicase family

Cited by 45 publications

References 61 publications

Sen1 Is Recruited to Replication Forks via Ctf4 and Mrc1 and Promotes Genome Stability

Sen1 Is Recruited to Replication Forks via Ctf4 and Mrc1 and Promotes Genome Stability

Termination of non‐coding transcription in yeast relies on both an RNA Pol II CTD interaction domain and a CTD‐mimicking region in Sen1

Termination of non-coding transcription in yeast relies on both a CTD-interaction domain and a CTD-mimic in Sen1

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