SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal domain control termination

Zhao, Dorothy Yanling; Gish, Gerald; Braunschweig, Ulrich; Li, Yue; Ni, Zuyao; Schmitges, Frank W.; Zhong, Guoqing; Liu, Ke; Li, Weiguo; Moffat, Jason; Vedadi, Masoud; Min, Jinrong; Pawson, Tony; Blencowe, Benjamin J.; Greenblatt, Jack

doi:10.1038/nature16469

Cited by 193 publications

(113 citation statements)

References 56 publications

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“…Analogously to S. cerevisiae Sen1, the human orthologue SETX has been proposed to play crucial roles in transcription termination and in the maintenance of genome integrity (Suraweera et al , 2009; Skourti‐Stathaki et al , 2011; Zhao et al , 2016). In line with its biological importance, mutations in SETX have been linked to two neurological disorders: ALS4 and AOA2.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2017

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The superfamily 1B (SF1B) helicase Sen1 is an essential protein that plays a key role in the termination of non‐coding transcription in yeast. Here, we identified the ~90 kDa helicase core of Saccharomyces cerevisiae Sen1 as sufficient for transcription termination in vitro and determined the corresponding structure at 1.8 Å resolution. In addition to the catalytic and auxiliary subdomains characteristic of the SF1B family, Sen1 has a distinct and evolutionarily conserved structural feature that “braces” the helicase core. Comparative structural analyses indicate that the “brace” is essential in shaping a favorable conformation for RNA binding and unwinding. We also show that subdomain 1C (the “prong”) is an essential element for 5′‐3′ unwinding and for Sen1‐mediated transcription termination in vitro. Finally, yeast Sen1 mutant proteins mimicking the disease forms of the human orthologue, senataxin, show lower capacity of RNA unwinding and impairment of transcription termination in vitro. The combined biochemical and structural data thus provide a molecular model for the specificity of Sen1 in transcription termination and more generally for the unwinding mechanism of 5′‐3′ helicases.

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Section: Resultsmentioning

confidence: 99%

“…Disease mutations cluster in the two most conserved regions of SETX, the N‐terminal domain and the helicase domain. Like its yeast orthologue, SETX has been assigned functions in transcription termination and in the control of R‐loop formation (Suraweera et al , 2009; Skourti‐Stathaki et al , 2011; Zhao et al , 2016). …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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“…SMN controls various aspects of the RNA metabolism, including but not limited to transcription [90], pre-mRNA splicing [106], snRNP assembly [20,72,108–115], the 3′ end of histone mRNA processing [116,117], snoRNP assembly [82,118,119], telomerase activity [119], SG formation [120], translation [121,122], signal recognition particle (SRP) biogenesis [123] and mRNA trafficking [124–130] (Fig. 3).…”

Section: Role Of Smn In Rna Metabolismmentioning

confidence: 99%

“…SMN may indirectly affect transcription-coupled splicing regulation through its interacting partners, such as FUS and helicases that associate with pol II [186]. Since SMN controls pausing at the transcription termination site [90], it may also modulate splicing of last introns by recruiting splicing factors during transcription termination.…”

Section: Role Of Smn In Rna Metabolismmentioning

confidence: 99%

“…Supporting the role of SMN in transcription termination, SMN interacts with Senataxin, a putative DNA/RNA helicase, which is involved in the resolution of R-loops [191]. More recently, a role for SMN in resolution of R-loops and transcription termination has been established through its direct interaction with the symmetrically dimethylated residues of the CTD of pol II [90]. …”

Section: Role Of Smn In Rna Metabolismmentioning

confidence: 99%

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Diverse role of survival motor neuron protein

Singh

Howell

Ottesen

et al. 2017

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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The multifunctional Survival Motor Neuron (SMN) protein is required for the survival of all organisms of the animal kingdom. SMN impacts various aspects of RNA metabolism through the formation and/or interaction with ribonucleoprotein (RNP) complexes. SMN regulates biogenesis of small nuclear RNPs, small nucleolar RNPs, small Cajal body-associated RNPs, signal recognition particles and telomerase. SMN also plays an important role in DNA repair, transcription, pre-mRNA splicing, histone mRNA processing, translation, selenoprotein synthesis, macromolecular trafficking, stress granule formation, cell signaling and cytoskeleton maintenance. The tissue-specific requirement of SMN is dictated by the variety and the abundance of its interacting partners. Reduced expression of SMN causes spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. SMA displays a broad spectrum ranging from embryonic lethality to an adult onset. Aberrant expression and/or localization of SMN has also been associated with male infertility, inclusion body myositis, amyotrophic lateral sclerosis and osteoarthritis. This review provides a summary of various SMN functions with implications to a better understanding of SMA and other pathological conditions.

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Writing a wrong: Coupled RNA polymerase II transcription and RNA quality control

et al. 2019

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Processing and maturation of precursor RNA species is coupled to RNA polymerase II transcription. Co‐transcriptional RNA processing helps to ensure efficient and proper capping, splicing, and 3′ end processing of different RNA species to help ensure quality control of the transcriptome. Many improperly processed transcripts are not exported from the nucleus, are restricted to the site of transcription, and are in some cases degraded, which helps to limit any possibility of aberrant RNA causing harm to cellular health. These critical quality control pathways are regulated by the highly dynamic protein–protein interaction network at the site of transcription. Recent work has further revealed the extent to which the processes of transcription and RNA processing and quality control are integrated, and how critically their coupling relies upon the dynamic protein interactions that take place co‐transcriptionally. This review focuses specifically on the intricate balance between 3′ end processing and RNA decay during transcription termination. This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Processing > 3' End Processing RNA Processing > Splicing Mechanisms RNA Processing > Capping and 5' End Modifications

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SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal domain control termination

Cited by 193 publications

References 56 publications

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

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

Diverse role of survival motor neuron protein

Writing a wrong: Coupled RNA polymerase II transcription and RNA quality control

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