ライフサイエンスコーパス: spliceosome

1 interactions with numerous components of the spliceosome.

2 quired to assemble galectin-3 onto an active spliceosome.

3 moved from their respective pre-mRNAs by the spliceosome.

4 dynamic protein-protein interactions of the spliceosome.

5 substrate RNA from the catalytic core of the spliceosome.

6 and introns are removed from pre-mRNA by the spliceosome.

7 t comprises a major subunit of the assembled spliceosome.

8 its overall connectivity to the rest of the spliceosome.

9 ctivation process and the active site of the spliceosome.

10 o transesterification steps catalyzed by the spliceosome.

11 ing the splicing cycle as carried out by the spliceosome.

12 ture and function relationships in the human spliceosome.

13 protein, a unique component of the U12-type spliceosome.

14 splice site complexes within the assembling spliceosome.

15 ibitor that targets the SF3B1 subunit of the spliceosome.

16 ng proposed to be the ribozyme progenitor of spliceosome.

17 small nuclear ribonucleoproteins (snRNPs) or spliceosome.

18 st potential tumour-promoting defects in the spliceosome.

19 trate that it physically associates with the spliceosome.

20 omal introns and other key components of the spliceosome.

21 like subfamily and an essential component of spliceosome.

22 ivity to pharmacological perturbation of the spliceosome.

23 d SNRNP200, it forms a central module of the spliceosome.

24 nctional interactions with components of the spliceosome.

25 ilitating the physical rearrangements of the spliceosome.

26 large ribonucleoprotein complex known as the spliceosome.

27 are highly plastic as compared to the major spliceosome.

28 nd localizes to nuclear speckles adjacent to spliceosomes.

29 iat spliceosomes (ILS) and defective earlier spliceosomes.

30 spliceostatin A (2) are potent inhibitors of spliceosomes.

31 ction from transposon transcripts stalled on spliceosomes.

32 e, which subsequently gets incorporated into spliceosomes.

33 or increases U2 snRNP recruitment, enhances spliceosome A complex formation, and facilitates exon de

34 Splicing is catalyzed by the spliceosome, a complex of five major small nuclear ribon

35 This process is mediated by the spliceosome, a large and dynamic RNA-protein machinery c

36 Precursor mRNA splicing is catalyzed by the spliceosome, a macromolecule composed of small nuclear R

37 pes, the molecular bases and consequences of spliceosome aberrations in cancer are poorly understood.

38 fter the first step of splicing (C), and the spliceosome activated for the second step (C*).

39 ure provides important new insights into the spliceosome activation process leading to the formation

40 uclear RNA-protein complex (di-snRNP) during spliceosome activation via ATP-driven translocation on t

41 e the key events in Saccharomyces cerevisiae spliceosome activation.

42 ndicating that both proteins may function in spliceosome activation.

43 sive exchange of proteins that occurs during spliceosome activation.

44 2-U6 helix I, all RNA elements that form the spliceosome active site.

45 , and transforms into a catalytically active spliceosome after extensive compositional and conformati

46 and that protein and metal cofactors of the spliceosome alter how snRNAs respond to these modificati

47 These findings make the spliceosome an attractive new target for small-molecule,

48 regulating levels of core components of the spliceosome and alternative splicing of downstream genes

49 An immune response directed against spliceosome and glycolysis proteins was observed with ca

50 n homologue C9ORF78 also associates with the spliceosome and is overexpressed in multiple cancer cell

51 However, the Prp43 binding site in the spliceosome and its target(s) are unknown.

52 NAs (snRNAs) are the basal components of the spliceosome and play essential roles in splicing.

53 RBM25 interacts with components of the early spliceosome and regulators of alternative splicing.

54 earrangements of RNP complexes including the spliceosome and ribosome.

55 protein factors work together to remodel the spliceosome and stabilize a conformation competent for 3

56 Patients with chromatin-spliceosome and TP53-aneuploidy AML had poor outcomes, w

57 g in Drosophila cells, we identify many core spliceosome and transcription termination factors that c

58 was associated primarily with the activated spliceosome and, accordingly, SPF27 silencing blocked th

59 induced circular RNAs processed by the minor spliceosome, and an enriched propensity of minor spliceo

60 ng: U1 small nuclear RNA, a component of the spliceosome, and Malat1, a large ncRNA that localizes to

61 ted with transmembrane transporter activity, spliceosome, and transcriptional regulation.

62 that conformational perturbations within the spliceosome are a naturally occurring and generalizable

63 NA and RNA-protein interactions in the minor spliceosome are highly plastic as compared to the major

64 ating that, in the absence of H2A.Z, stalled spliceosomes are disassembled, and unspliced RNAs are re

65 e U4 and U6 snRNAs are incorporated into the spliceosome as a base-paired complex within the U4/U6.U5

66 this active site configuration exists in the spliceosome as well.

67 elopment to target altered dependency on the spliceosome, as well as aberrant splicing, in cancer.

68 ols with which to probe different aspects of spliceosome assembly and function.

69 rs, such as SR proteins and hnRNPs, modulate spliceosome assembly and regulate alternative splicing.

70 ns to stabilize weak U2/BS duplexes to drive spliceosome assembly and splicing.

71 Madrasin interferes with the early stages of spliceosome assembly and stalls spliceosome assembly at

72 These data suggest that early stages of spliceosome assembly are sufficient to functionally coup

73 MBNL1 enhances early spliceosome assembly as evidenced by enhanced complex A

74 ly stages of spliceosome assembly and stalls spliceosome assembly at the A complex.

75 indicate that the U2AF heterodimer promotes spliceosome assembly by a dynamic population shift towar

76 showed accumulation of the kinase into large spliceosome assembly factor-positive speckle domains wit

77 able exon region of CD44 pre-mRNA to inhibit spliceosome assembly in favor of expressing the mesenchy

78 cing are important tools for identifying new spliceosome assembly intermediates, allowing a finer dis

79 t bring the two splice sites together during spliceosome assembly must occur with a high degree of sp

80 Perturbations that slow the rate of spliceosome assembly or speed up the rate of transcripti

81 spliceosome component PRPF8 is essential for spliceosome assembly through its participation in ribonu

82 s from pre-messenger RNA (pre-mRNA) requires spliceosome assembly with pre-mRNA, then subsequent spli

83 ith Prp5p, the first ATPase that acts during spliceosome assembly, and localized the interacting regi

84 Stem IIa forms during spliceosome assembly, and stem IIc forms during the cata

85 oprotein (snRNP) biogenesis is essential for spliceosome assembly, but not well understood.

86 splicing during the exon definition phase of spliceosome assembly, but the assembly steps leading to

87 tudies provide mechanistic insights into how spliceosome assembly, dynamics, and catalysis occur; how

88 avone inhibits splicing in vitro by blocking spliceosome assembly, preventing formation of the B comp

89 During spliceosome assembly, protein-protein interactions (PPI)

90 ative to wild type, resulting in inefficient spliceosome assembly.

91 ired to unwind the U4/U6 snRNA duplex during spliceosome assembly.

92 plays important roles during early steps of spliceosome assembly.

93 domain and has been shown to participate in spliceosome assembly.

94 licing inhibitor that blocks a late stage of spliceosome assembly.

95 tors that interfere with different stages of spliceosome assembly.

96 liceosome formation during cotranscriptional spliceosome assembly.

97 ndicating a requirement for a SL4 contact in spliceosome assembly.

98 wn to bind pre-mRNA at the earliest stage of spliceosome assembly.

99 ing, mostly by disrupting multiple stages of spliceosome assembly.

100 cient splice-site recognition and subsequent spliceosome assembly.

101 of 3'-splice site during the early stages of spliceosome assembly; however, its precise role in RNA s

102 The endonuclease CPSF3 (CPSF73) and the spliceosome-associated ISY1 are responsible for pro-miRN

103 on and splicing (RES) complex is a conserved spliceosome-associated module that was shown to enhance

104 Here we report that defects in spliceosome-associated protein CWC27 are associated with

105 Here we identify two spliceosome-associated proteins-SAP145 and SAP49-as PRMT

106 haromyces cerevisiae pre-catalytic B complex spliceosome at near-atomic resolution.

107 Analysis of the cryo-EM spliceosome B(act) complex shows that the resistance mut

108 e.g., the fully assembled but not yet active spliceosome (Bact), the spliceosome just after the first

109 synthetic lethal with inhibition of the core spliceosome, because MYC-driven growth and increased tra

110 i-snRNP represents a substantial part of the spliceosome before activation.

111 NA, these introns must be removed within the spliceosome before export of the processed mRNA to the c

112 The ATPase Prp16 remodels the spliceosome between the first and second steps of splici

113 uires close apposition of intron ends by the spliceosome, but when and how apposition occurs is uncle

114 odulate the ATPase activity of Prp16p in the spliceosome by controlling access to its RNA substrate/c

115 In this fashion, Brr2 can activate the spliceosome by stripping U6 snRNA of all precatalytic bi

116 mic profiling, we showed that JA targets the spliceosome by up-regulating SF3B1 and SF3B3 protein in

117 We propose that the spliceosome can also repress protein-coding gene express

118 ndrial organelle suggest that nuclei-encoded spliceosome can mediate splicing of mtRNA.

119 30 years of genetics and biochemistry of the spliceosome can now be interpreted at the structural lev

120 mic ribonucleic protein machine known as the spliceosome catalyzes the removal of introns from premes

121 We identified a specificity for the minor spliceosome complex containing RNA Binding Region (RNP1,

122 Isolation of early spliceosome complex revealed that the mutation impairs b

123 r of the tri-snRNP (small ribonucleoprotein) spliceosome complex, drives cancer proliferation by pref

124 tures of B, B(act), C, C*, and intron lariat spliceosome complexes revealed mechanisms of 5'-splice s

125 -snRNP complex proteins, but not other snRNP spliceosome complexes, selectively abrogated growth in c

126 alysis of a hypomorphic mutation in the core spliceosome component PRP8.

127 The core spliceosome component PRPF8 is essential for spliceosome

128 Mutations in SF3B1, which encodes a spliceosome component, are associated with poor outcome

129 ted the disruptive impact of mutated generic spliceosome components and splicing regulatory proteins.

130 the database provides an easy reference for spliceosome components and will support future modeling

131 by forming multiple interactions with early spliceosome components bound proximal to 3' splice sites

132 We propose that spliceosome components contribute to sister chromatid co

133 While somatic mutations in spliceosome components have been discovered in several c

134 Genetic defects in several spliceosome components have been linked to a set of non-

135 mutations (75%), we identified mutations in spliceosome components in 88%, including SRSF2 codon 95

136 de links to gene and protein records for the spliceosome components in other databases.

137 vity and suggest that modulation of specific spliceosome components may prolong healthy ageing.

138 iCLIP of spliceosome components reveals that PRPF8 depletion decr

139 ent a model where Nab2/ZC3H14 interacts with spliceosome components to allow proper coupling of splic

140 When spliceosome components were depleted or inhibited pharma

141 iabilities Owing to Partial losS) genes, and spliceosome components were the most prevalent.

142 of comutations in epigenetic regulators and spliceosome components, and how these mutations cooperat

143 INTERPRETATION: Interference with particular spliceosome components, including small nuclear RNAs, ca

144 t aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b

145 d that FgPrp4, the only protein kinase among spliceosome components, is important for intron splicing

146 everal genes encoding components of the core spliceosome composed of a heteroheptameric Sm complex we

147 biasing the relative stabilities of distinct spliceosome conformations.

148 The active centre of the spliceosome consists of an intricate network formed by U

149 in all complexes by Prp43_Ntr1GP, and in the spliceosome contacts U2 proteins and the pre-mRNA, indic

150 ysis and that this constraint is overcome in spliceosomes containing mutant SF3B1.

151 Here, we determine whether the spliceosome could constitute an attractive therapeutic t

152 We identify a Spliceosome-Coupled And Nuclear RNAi (SCANR) complex req

153 icing complexes at distinct stages along the spliceosome cycle.

154 ar at distinct times during development in a spliceosome-dependent and transcription-independent mann

155 ished role in assembling constituents of the spliceosome, diverse cellular functions have been propos

156 ceosome, and an enriched propensity of minor spliceosome donors to splice into circular RNA at un-ann

157 x reveals the two major conformations of the spliceosome during the catalytic stages of splicing.

158 ntermediates, allowing a finer dissection of spliceosome dynamics and function.

159 ranslational modifications contribute to the spliceosome dynamics by facilitating the physical rearra

160 ator of protein-protein interactions for the spliceosome dynamics.

161 The U12-dependent minor spliceosome edits 879 known transcripts.

162 owing binding of the U4/U6.U5 tri-snRNP, the spliceosome either reverses assembly by discarding tri-s

163 er to our view of how the eukaryotic nuclear spliceosome evolved after bacterial endosymbiosis throug

164 The spliceosome excises introns from pre-mRNAs in two sequen

165 s not require U2AF2, a core component of the spliceosome, for its processing.

166 utant molecules and proteins associated with spliceosome formation (U2AF35, U2AF65, U1A, and U1-70K)

167 sites across an intron is a critical step in spliceosome formation and its regulation.

168 U6 rearrangements are crucial for spliceosome formation but are poorly understood.

169 By using metal rescue strategies in spliceosomes from budding yeast, here we show that the U

170 oding RNAs, leading to the redistribution of spliceosomes from this abundant class of intron-containi

171 expression, leading to the redistribution of spliceosomes from this abundant class of intron-containi

172 iption of ETS family target genes related to spliceosome function and cell death induction via altern

173 Modulation of spliceosome function may thus provide a new therapeutic

174 ese results demonstrate a conserved role for spliceosomes functioning in 3' end processing.

175 The observation that the spliceosome functions in 3' end processing raised questi

176 We hypothesize that cells harbouring spliceosome gene mutations have increased sensitivity to

177 Although DNA sequencing has uncovered spliceosome gene mutations that promote alternative spli

178 Heterozygous somatic mutations in the spliceosome gene U2AF1 occur in approximately 11% of pat

179 Somatic mutations in the spliceosome gene ZRSR2-located on the X chromosome-are a

180 We now present data in support of spliceosomes generating 3' ends of telomerase RNAs in ot

181 Somatic mutations in spliceosome genes are detectable in approximately 50% of

182 so had less mutations in the methylation and spliceosome groups compared with patients >/=60 years of

183 ions in SETBP1, epigenetic modifiers, or the spliceosome has been determined only in isolated case re

184 to individual snRNPs, purification of intact spliceosomes has not been achieved yet.

185 Mutations in components of the major spliceosome have been described in disorders with cranio

186 are required for disassembling intron-lariat spliceosomes (ILS) and defective earlier spliceosomes.

187 microscopy structure of the yeast P-complex spliceosome immediately after exon ligation.

188 A cryo-electron microscopy structure of the spliceosome immediately after lariat formation.

189 t to normal cells, partial inhibition of the spliceosome in MYC-hyperactivated cells leads to global

190 which are removed from precursor RNAs by the spliceosome in two sequential but tightly coupled transe

191 m eukaryotic messenger RNA precursors by the spliceosome in two transesterification reactions-branchi

192 genetic or pharmacological inhibition of the spliceosome in vivo impairs survival, tumorigenicity and

193 is the responsibility of the major and minor spliceosomes in collaboration with numerous splicing fac

194 Spliceosome inhibition resulted in the accumulation of h

195 the context of leukemia, treatment with the spliceosome inhibitor E7107 (refs.

196 thod was applied to a rapid synthesis of the spliceosome inhibitor herboxidiene.

197 The total synthesis of the spliceosome inhibitor thailanstatin A has been achieved

198 Spliceostatins are potent spliceosome inhibitors biosynthesized by a hybrid nonrib

199 However, the current collection of spliceosome inhibitors is very limited.

200 RCA1, both in vitro and in vivo Furthermore, spliceosome inhibitors reduced BRCA1-Delta11q levels and

201 ndustrial efforts to develop natural product spliceosome inhibitors, including FD-895 (1a), pladienol

202 New structures of spliceosome intermediates and associated protein complex

203 ation of catalytic core of the U12-dependent spliceosome involves U6atac and U12 interaction with the

204 The spliceosome is a complex machine composed of small nucle

205 The spliceosome is a dynamic complex of five structural RNAs

206 The spliceosome is a huge molecular machine that assembles d

207 The human spliceosome is a large ribonucleoprotein complex that ca

208 Here we discover that the spliceosome is a new target of oncogenic stress in MYC-d

209 After assembly the spliceosome is activated for catalysis by rearrangement

210 ar ribonucleic acid (snRNA) component of the spliceosome is targeted for additional post-transcriptio

211 The spliceosome is the extremely complex macromolecular mach

212 otic retroelements, including telomeres, and spliceosomes is unmistakable.

213 d but not yet active spliceosome (Bact), the spliceosome just after the first step of splicing (C), a

214 ccompanied by the formation of a chloroplast spliceosome-like machinery.

215 cogenic candidate, SNRPB, which encodes core spliceosome machinery components.

216 The spliceosome machinery is composed of multimeric protein

217 The spliceosome machinery is composed of several proteins an

218 and of core components of the nuclei-encoded spliceosome machinery within the mitochondrial organelle

219 regulatory potential of changes in the core spliceosome machinery, which may be relevant to slow-ons

220 ress on splicing, and that components of the spliceosome may be therapeutic entry points for aggressi

221 Furthermore, interactions with the spliceosome may contribute to repression by Gro.

222 ition to the second step conformation of the spliceosome, mediated through its interactions with the

223 The mechanism underlying spliceosome-mediated 3' end processing has remained uncl

224 Here we report a unique spliceosome-mediated TER 3'-end cleavage mechanism in Ne

225 tion and development of small molecules with spliceosome-modulating activity as potential anticancer

226 San Diego has undertaken a SAR study on the spliceosome modulator FD-895 that focused on improving c

227 Furthermore, the spliceosome modulator, E7017, selectively kills SF3B1(K7

228 and prognostic tools and the availability of spliceosome modulators opens novel therapeutic prospects

229 ster linkages in RNA lariats produced by the spliceosome must be hydrolyzed by the intron debranching

230 In doing so, the spliceosome must distinguish optimal from suboptimal spl

231 The spliceosome must identify the correct splice sites (SS)

232 Spliceosomes must ensure accurate removal of highly dive

233 patients >/=60 years of age, the presence of spliceosome mutations associated with a lower complete r

234 factor gene IFH1 genetically suppresses two spliceosome mutations, prp11-1 and prp4-1, and globally

235 onical splicing events involving U2- and U12 spliceosomes occur within nuclear pre-mRNAs.

236 Intron removal requires assembly of the spliceosome on precursor mRNA (pre-mRNA) and extensive r

237 Sequential assembly of the human spliceosome on RNA transcripts regulates splicing across

238 ssential early step in the assembly of human spliceosomes onto pre-mRNA involves the recognition of r

239 vents NTR from disrupting properly assembled spliceosomes other than the ILS.

240 The spliceosome plays a fundamental role in RNA metabolism b

241 Together, these data suggest the spliceosome possesses far lower fidelity than previously

242 E complex is the earliest spliceosome precursor in which the 5' SS and BS are defi

243 d in RNA-binding motif protein 20 (RBM20), a spliceosome protein induced during early cardiogenesis.

244 to the carboxy-terminal domain of the yeast spliceosome protein PRP18, which stabilizes specific pro

245 e commonalities include mutations in SETBP1, spliceosome proteins (SRSF2, U2AF1), and epigenetic modi

246 rs transcription elongation, suggesting that spliceosome rearrangements are tied to H2A.Z's role in e

247 These alleles change how the spliceosome recognizes the BS and alter splicing when no

248 ma antigen recognized by T-cell 3 (SART3), a spliceosome recycling factor, binds to the DUSP-UBL doma

249 XRN2 in the same complexes along with other spliceosome-related proteins.

250 ose that Cwc2 is a target for Prp16-mediated spliceosome remodeling during pre-mRNA splicing.

251 Spliceosome remodeling is carried out through the action

252 some assembly with pre-mRNA, then subsequent spliceosome remodeling to allow activation for the two s

253 r RNAs (mRNAs) via RNA splicing, whereby the spliceosome removes non-coding introns from pre-mRNAs an

254 ules that target different components of the spliceosome represent valuable research tools to investi

255 strate that BUD31 is a component of the core spliceosome required for its assembly and catalytic acti

256 ucleoprotein machines, such as ribosomes and spliceosomes, RNA functions as an assembly scaffold as w

257 in order for U6 to pair with U2 to form the spliceosome's active site.

258 -mRNA) and extensive remodelling to form the spliceosome's catalytic centre.

259 lace the RNaseH domain (RH) of Prp8 near the spliceosome's catalytic core and demonstrate that prp8 a

260 , we discovered that the low abundance minor spliceosome's catalytic snRNP, U6atac, is strikingly uns

261 However, the mechanism by which the spliceosome selects only certain exons to circularize is

262 sion and regulation of eukaryotic genes, the spliceosome selects splice sites for intron excision and

263 dings indicate that group II introns and the spliceosome share common catalytic mechanisms and probab

264 A viral transcriptome including the viral spliceosome should be evaluated to gain new insights int

265 r, we detected 5'splice site cleavage by the spliceosome, showing that cleaved upstream exon transcri

266 ound in Prp3 orthologs, thus qualifying as a spliceosome-specific RNA interaction module.

267 ion of U6atac snRNA contains a U12-dependent spliceosome-specific targeting activity.

268 ith RNA polymerase III (POLR3) and the minor spliceosome specificities.

269 y of circular RNA production occurs at major spliceosome splice sites; however, we find the first exa

270 copy structure of a Saccharomyces cerevisiae spliceosome stalled after Prp16-mediated remodelling but

271 dependent splicing repression occurs through spliceosome stalling at complex A.

272 mponents and will support future modeling of spliceosome structure and dynamics.

273 ears have led to the solution of a number of spliceosome structures at high resolution, e.g., the ful

274 proteins show that Tls1 associates with the spliceosome subunit Brr2.

275 iciency of SMN protein, which is crucial for spliceosome subunits biogenesis.

276 Loss of spliceosome subunits increases the dissociation rate of

277 Based on structural homology with other spliceosome subunits, and recent findings of altered RNA

278 rs, including the U5 snRNP components of the spliceosome, such as EFTUD2.

279 the U5 snRNP200 complex, a component of the spliceosome that in normal cells is found in the cell.

280 th a particular focus on the major and minor spliceosome, the factors controlling RNA splicing, and t

281 een considered the "master regulator" of the spliceosome, the molecular machine that executes pre-mRN

282 the nascent snRNA during its journey to the spliceosome.The mechanism of U6 small nuclear ribonucleo

283 the evolutionary ancestors of the eukaryotic spliceosome, thus representing an ideal model system to

284 w they differentially interact with the core spliceosome to perform their functions.

285 , suggesting an increased burden on the core spliceosome to process pre-mRNA.

286 ng and a deeply conserved role for the minor spliceosome to promote cell differentiation from stem ce

287 ese ATPases function further by enabling the spliceosome to search for and utilize alternative branch

288 We hypothesize that the spliceosome "toggles" between such error-prone/efficient

289 odeling, cohesin complex, methylation, NPM1, spliceosome, transcription factors, and tumor suppressor

290 ZRSR2 as an essential component of the minor spliceosome (U12 dependent) assembly.

291 small nuclear RNA (snRNA) components of the spliceosome undergo many conformational rearrangements d

292 The spliceosome undergoes dramatic changes in a splicing cyc

293 to facilitate the conformational changes the spliceosome undergoes during catalysis.

294 ctivity of SR and hnRNP proteins to the core spliceosome using probabilistic network reconstruction b

295 has focused on the Saccharomyces cerevisiae spliceosome, viewed as a highly simplified system with f

296 The spliceosome was targeted by small interfering RNA-mediat

297 We identified that QKI localizes to the spliceosome, where it interacts with the myocardin pre-m

298 dynamic ribonucleoprotein complex termed the spliceosome, which is composed of five small nuclear rib

299 Targeting the spliceosome with small molecule inhibitors provides a ne

300 RNA and protein components of the spliceosome work together to identify the 5 splice site,