The sen1+ Gene of Schizosaccharomyces pombe, a Homologue of Budding Yeast SEN1, Encodes an RNA and DNA Helicase

Kim, Hee-Dai; Choe, Joonho; Seo, Yeon‐Soo

doi:10.1021/bi991470c

Cited by 98 publications

(92 citation statements)

References 48 publications

(88 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with the reported activity of native Sen1 purified from S. pombe (18), S. cerevisiae Sen1-HD has 5Ј-to 3Ј-helicase activity (Fig. 4).…”

Section: Discussionsupporting

confidence: 89%

“…Previously, a 5Ј-to 3Ј-RNA and DNA helicase activity purified from Schizosaccharomyces pombe cell extract was attributed to an ortholog of S. cerevisiae Sen1 (18). More recently, however, TAP-tagged Sen1 purified from S. cerevisiae exhibited no DNA/RNA duplex unwinding activity and did not stably bind RNA, despite having DNA-and RNA-dependent ATPase activity (19).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Saccharomyces cerevisiae Sen1 Helicase Domain Exhibits 5′- to 3′-Helicase Activity with a Preference for Translocation on DNA Rather than RNA

Martin-Tumasz

Brow

2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Yeast Sen1 helicase and its human ortholog senataxin promote accurate transcription termination. Results: Sen1 helicase domain exhibits 5Ј-to 3Ј-helicase activity on DNA and RNA and binds endogenous RNA. Conclusion: Biochemical activities of purified Sen1 helicase domain are consistent with its proposed function in resolving cotranscriptional R-loops. Significance: Mutations in senataxin and its paralog IGHMBP2 cause crippling neurodegenerative diseases.

show abstract

“…Consistent with the reported activity of native Sen1 purified from S. pombe (18), S. cerevisiae Sen1-HD has 5Ј-to 3Ј-helicase activity (Fig. 4).…”

Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

Saccharomyces cerevisiae Sen1 Helicase Domain Exhibits 5′- to 3′-Helicase Activity with a Preference for Translocation on DNA Rather than RNA

Martin-Tumasz

Brow

2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…In addition to establishing that HCoV p66 HEL is an SF1 RNA helicase, we have shown that it differs significantly from the previously characterized SF2 RNA virus helicases+ Thus, although all RNA virus helicases investigated so far operate in 39-to-59 direction (reviewed in Kadaré & Haenni, 1997), the coronavirus RNA duplex-unwinding activity has 59-to-39 polarity+ This finding implies that the coronavirus helicase binds to the 59 single-stranded region of a partial-duplex RNA and unwinds this duplex in a 59-to-39 direction with respect to the RNA strand used for entry+ In this context, it will be important to find out whether the difference in the polarity of the unwinding process between the coronavirus helicase and RNA viral SF2 helicases also reflects a fundamental difference between SF1 and SF2 helicases, that is, do other RNA viral SF1 helicases share the 59-to-39 polarity with the coronavirus helicase+ The only other RNA viral SF1 helicase activity reported so far, that of the Semliki Forest virus nsp2 protein, showed extremely low duplex-unwinding activity in vitro and, to our knowledge, has not yet been characterized with regard to its polarity (Gomez de Cedrón et al+, 1999)+ Studies on molecular motors of the kinesin superfamily (Henningsen & Schliwa, 1997) have demonstrated that the specific arrangement of motor domains with their associated accessory domains may determine the polarity of translocation+ It is therefore con- ceivable that the directionality of helicases may also be controlled by additional domains rather than by the intrinsic properties of the core helicase itself+ Indeed, numerous cellular helicases carry additional nucleic acid-binding domains, including zinc finger structures (reviewed in Gorbalenya & Koonin, 1993)+ Most of these additional domains are either attached to one or the other of the core helicase termini, or they are inserted between the helicase motifs Ia and II or IV and V, respectively (Gorbalenya & Koonin, 1993;Bird et al+, 1998)+ Obviously, it will be interesting to examine if the amino terminal zinc finger contributes to the function of the coronavirus helicase+ Furthermore, the possibility that there are additional contacts between the HCoV enzyme and the duplex region of the substrate needs to be investigated+ Such interactions have recently been postulated to be of critical importance for the duplexunwinding activity of the bacterial DNA helicase PcrA (Velankar et al+, 1999)+ Another important finding of this study is the apparent lack of specificity of the coronavirus helicase for RNA versus DNA substrates+ The vast majority of helicases act in a very specific manner on either RNA or DNA+ The few enzymes that lack this specificity (Stahl et al+, 1986;Scheffner et al+, 1989;Zhang & Grosse, 1994;Bayliss & Smith, 1996;Gwack et al+, 1997;Laxton et al+, 1998;Costa et al+, 1999;Kim et al+, 1999) are mainly virus encoded or so-called noncanonical helicases+ Structural data on one of these enzymes, HCV NS3, have recently shown that the primary interactions between NS3 and the single-stranded substra...…”

Section: Biochemical Properties Of the Hcov Helicasementioning

confidence: 80%

The human coronavirus 229E superfamily 1 helicase has RNA and DNA duplex-unwinding activities with 5′-to-3′ polarity

Seybert

Hegyi

Siddell

et al. 2000

RNA

144

181

View full text Add to dashboard Cite

The human coronavirus 229E replicase gene encodes a protein, p66 HEL , that contains a putative zinc finger structure linked to a putative superfamily (SF) 1 helicase. A histidine-tagged form of this protein, HEL, was expressed using baculovirus vectors in insect cells. The purified recombinant protein had in vitro ATPase activity that was strongly stimulated by poly(U), poly(dT), poly(C), and poly(dA), but not by poly(G). The recombinant protein also had both RNA and DNA duplex-unwinding activities with 59-to-39 polarity. The DNA helicase activity of the enzyme preferentially unwound 59-oligopyrimidine-tailed, partial-duplex substrates and required a tail length of at least 10 nucleotides for effective unwinding. The combined data suggest that the coronaviral SF1 helicase functionally differs from the previously characterized RNA virus SF2 helicases.

show abstract

“…1e), and so we named it senataxin (SETX). Saccharomyces cerevisiae Sen1p is involved in splicing and termination of tRNA, small nuclear RNA and small nucleolar RNA and has RNA helicase activity encoded by its C-terminal domain [7][8][9] . Schizosaccharomyces pombe has two Sen1 genes.…”

mentioning

confidence: 99%

“…Schizosaccharomyces pombe has two Sen1 genes. The first reported S. pombe Sen1p (Sen1p1, encoded on chromosome I) has both RNA and DNA helicase activities 9 . Of all the fungal Sen1p proteins, however, the second S. pombe Sen1p (Sen1p2, encoded on chromosome II) has the highest homology with senataxin over the N-terminal domain (20% identity over 466 residues).…”

mentioning

confidence: 99%

Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2

et al. 2004

View full text Add to dashboard Cite

Ataxia-ocular apraxia 2 (AOA2) was recently identified as a new autosomal recessive ataxia. We have now identified causative mutations in 15 families, which allows us to clinically define this entity by onset between 10 and 22 years, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia and elevated alpha-fetoprotein (AFP). Ten of the fifteen mutations cause premature termination of a large DEAxQ-box helicase, the human ortholog of yeast Sen1p, involved in RNA maturation and termination.We previously identified a 16-cM interval on chromosome 9q34 associated with an autosomal recessive adolescent-onset cerebellar ataxia segregating in two families 1,2 , one with additional oculomotor apraxia 1 and the second with associated elevated serum AFP, immunoglobulins and creatine kinase levels but no oculomotor apraxia 2,3 . We identified nine additional families with ataxia linked to 9q34 by homozygosity mapping (Supplementary Methods online). As most affected individuals had both oculomotor apraxia and elevated AFP levels we assumed that they were affected by the same disorder, which we named AOA2 (OMIM 606002). We identified distal and proximal recombinations in families with two affected individuals (Fig. 1a), localizing the defective gene underlying AOA2 to a 1.1-Mb interval containing 13 genes ( Fig. 1b) and three groups of overlapping spliced expressed-sequence tags, which we analyzed for nucleotide changes but found no mutations. We also found that the unspliced mRNA AK024331 overlaps with the KIAA0625 cDNA and is part of a larger transcript overlapping with additional exons on the 5′ side. We obtained an open reading frame of 8,031 nucleotides and 24 exons (Fig. 1c), of which exon 8 was 4,177 nucleotides long. We confirmed the prediction and size of the transcript by long-range RT-PCR experiments spanning the putative exon 1 and 3′ untranslated region in human fibroblast and lymphoblastoid cell lines (data not shown) and by hybridization of a human northern blot with a probe spanning putative exons 8-24 (Fig. 1d). We also identified an alternative transcript that is 2.4 kb longer, resulting from a second polyadenylation site (human mRNAs AB014525 and AK022902; Fig. 1d).We sequenced exons 1-18 and flanking intronic sequences in families with ataxia linked to this region and in additional individuals with either AOA or ataxia with elevated AFP levels and found 15 different disease-associated mutations in 15 families ( Table 1). Ten of these mutations, including mutations in the two families in whom we first identified AOA2, cause truncation of the protein, indicating that this is the gene underlying AOA2. We found the nonsense mutation R1363X in three unrelated families originating from Portugal, Cabo Verde (once a Portuguese colony) and Spain, suggestive of an Iberian founder event, although recurrent C→T changes on this CpG dinucleotide cannot be formally excluded. Absence of the five missense mutations in 150 unrelated and unaffected individuals sharing the same ethnic origin as the affected in...

show abstract

The sen1⁺ Gene of Schizosaccharomyces pombe, a Homologue of Budding Yeast SEN1, Encodes an RNA and DNA Helicase

Cited by 98 publications

References 48 publications

Saccharomyces cerevisiae Sen1 Helicase Domain Exhibits 5′- to 3′-Helicase Activity with a Preference for Translocation on DNA Rather than RNA

Saccharomyces cerevisiae Sen1 Helicase Domain Exhibits 5′- to 3′-Helicase Activity with a Preference for Translocation on DNA Rather than RNA

The human coronavirus 229E superfamily 1 helicase has RNA and DNA duplex-unwinding activities with 5′-to-3′ polarity

Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2

Contact Info

Product

Resources

About