ライフサイエンスコーパス: spliceosome

1 all nuclear ribonucleoprotein (snRNP) of the spliceosome.

2 would disturb function of both Prp8 and the spliceosome.

3 facilitate the docking of tri-snRNP into the spliceosome.

4 have been shown to be specific to the minor spliceosome.

5 odeling, leading up to assembly of the early spliceosome.

6 ear ribonucleoprotein (snRNP) complex of the spliceosome.

7 om the B(act) to the catalytically active B* spliceosome.

8 U6 snRNA to form the catalytic center of the spliceosome.

9 form the fully assembled precatalytic pre-B spliceosome.

10 like subfamily and an essential component of spliceosome.

11 dynamic protein-protein interactions of the spliceosome.

12 omal introns and other key components of the spliceosome.

13 ivity to pharmacological perturbation of the spliceosome.

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

15 nctional interactions with components of the spliceosome.

16 ilitating the physical rearrangements of the spliceosome.

17 large ribonucleoprotein complex known as the spliceosome.

18 are highly plastic as compared to the major spliceosome.

19 interactions with numerous components of the spliceosome.

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

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

22 substrate RNA from the catalytic core of the spliceosome.

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

24 t comprises a major subunit of the assembled spliceosome.

25 ing regulators mostly connected to the major spliceosome.

26 sidered to be an artifact of a dysfunctional spliceosome.

27 sociated with messenger RNA splicing via the spliceosome.

28 in the 3' to 5' direction on remodeling the spliceosome.

29 ng evidence for a retroelement origin of the spliceosome.

30 th potential functional implications for the spliceosome.

31 ior to incorporation into the active site of spliceosomes.

32 e, which subsequently gets incorporated into spliceosomes.

33 nd localizes to nuclear speckles adjacent to spliceosomes.

34 iat spliceosomes (ILS) and defective earlier spliceosomes.

35 BP adenosine) more frequently than wild-type spliceosomes.

36 somal protein, SUGP1, were reduced in mutant spliceosomes.

37 lated SF3b(10), but a closed conformation in spliceosomes(11), which is required for stable interacti

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

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

40 cells, pre-mRNA splicing is catalyzed by the spliceosome, a highly dynamic molecular machinery that u

41 ntron, tightly correlating Srsf10 with minor spliceosome abundance across different tissues and diffe

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

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

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

45 sive exchange of proteins that occurs during spliceosome activation.

46 e the key events in Saccharomyces cerevisiae spliceosome activation.

47 results demonstrate that SME1 regulates the spliceosome activity and that this regulation is control

48 nteraction with the environment by providing spliceosome activity specificity.

49 lying a requirement for stringent control of spliceosome activity within the cell.

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

51 ns can work as non-coding RNAs that trap the spliceosome and decrease global splicing upon nutrient d

52 zed remain associated with components of the spliceosome and differ from other spliceosomal introns i

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

54 e in branchsite recognition, into the mutant spliceosome and partially rescued splicing.

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

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

57 of single hairpin RNAs that modify both the spliceosome and ribosome RNAs is unique for these parasi

58 er SR proteins also correlate with the minor spliceosome and Srsf10, and abolishing Srsf10 autoregula

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

60 along U6 from the 3' end to disassemble the spliceosome and thereby release suboptimal substrates or

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

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

63 aced before the stable addition of U2 to the spliceosome, and identify RNP rearrangements facilitated

64 ein processing in the endoplasmic reticulum, spliceosome, and mRNA processing.

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

66 Components of the spliceosome are frequently mutated in haematopoietic mal

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

68 our data show that the RNA components of the spliceosome are not merely basal factors, as has long be

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

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

71 ics and exome sequencing further support the spliceosome as a specific vulnerability in myeloma.

72 as a hallmark of PCa aggressiveness and the spliceosome as a therapeutic vulnerability for CRPC.

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

74 Spliceosomes assemble onto pre-mRNA guided by specific s

75 eotides with non-specific sequences restores spliceosome assembly and normal splicing, arguing agains

76 The ATPase Prp5p is required for pre-spliceosome assembly and splicing proofreading at the br

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

78 nd U2AF2 pre-mRNA splicing factors nucleates spliceosome assembly at polypyrimidine (Py) signals prec

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

80 e critical elongation enabling (inefficient) spliceosome assembly for EMD intron 5.

81 RNA splicing and spliceosome assembly in eukaryotes occur mainly during t

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

83 We propose that BS recognition during spliceosome assembly involves a set of coordinated confo

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

85 t that phytochromes target the early step of spliceosome assembly via a cascade of protein-protein in

86 ructure, transcriptional regulation, RNA pre-spliceosome assembly, and DNA damage.

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

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

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

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

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

92 e to biophysical constraint precluding U1/U2 spliceosome assembly, which stalls in A-complexes (that

93 ween Prp5 re-binding and subsequent steps in spliceosome assembly.

94 the intron branch site (BS) sequence during spliceosome assembly.

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

96 cient splice-site recognition and subsequent spliceosome assembly.

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

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

99 plays important roles during early steps of spliceosome assembly.

100 idine-tract splice-site signal and initiates spliceosome assembly.

101 transcription initiation/elongation and pre-spliceosome assembly.

102 to define 3' splice sites at early stages of spliceosome assembly.

103 tor-associated protein (STRAP) as a putative spliceosome-associated factor.

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

105 and the main target of SC35 mAb is SRRM2, a spliceosome-associated protein that sharply localizes to

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 This mechanism reveals that the spliceosome becomes primed for termination at the same s

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 (BRR2) is required for the activation of the spliceosome before the first catalytic step of RNA splic

113 mal components and structural changes of the spliceosome between steps, but information on how the pr

114 atively spliced genes, splice junctions, and spliceosome-bound sites) and transcription factor bindin

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 II transcribed snRNAs of the major and minor spliceosomes by removing posttranscriptional oligo(A) ta

118 vents in fam50a KO, suggesting a role in the spliceosome C complex.

119 ding proteins that function primarily in the spliceosome C complex.

120 mutated, as in many hereditary diseases, the spliceosome can aberrantly select nearby pseudo- or "cry

121 complex architecture suggests that the same spliceosome can assemble across an exon, and that it eit

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

123 30 years of genetics and biochemistry of the spliceosome can now be interpreted at the structural lev

124 RNA splicing, the spliceosome-catalyzed process by which pre-messenger RNA

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

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

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

128 ice sites and identified two alleles in core spliceosome component Prp8 that alter cryptic splicing f

129 In addition, we focus on spliceosome component SF3B1, which is mutated in many ty

130 g complex and facilitates recruitment of the spliceosome component U1 snRNP to cognate intronic posit

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

132 dysregulation in the expression of relevant spliceosome components and splicing factors (at mRNA and

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

134 BR5 in B-cell maturation by stabilization of spliceosome components during B-cell development and sug

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

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

137 ed biallelic mutations in genes encoding the spliceosome components Peptidyl-Prolyl Isomerase Like-1

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

139 When spliceosome components were depleted or inhibited pharma

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

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

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

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

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

145 als is linked to positive selection in minor spliceosome components.

146 Spliceosomes comprise small nuclear (sn)RNAs and protein

147 biasing the relative stabilities of distinct spliceosome conformations.

148 The spliceosome consists of five small RNAs and more than 10

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 Minor and major spliceosomes control splicing of distinct intron types a

152 lease excised introns in a manner coupled to spliceosome disassembly, thereby allowing recycling.

153 How the spliceosome distinguishes authentic splice sites from cr

154 Disruption of the minor spliceosome due to mutations in RNU4ATAC is linked to pr

155 stabilize the catalytic conformation of the spliceosome during exon ligation.

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

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

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

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

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

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

162 s and auxiliary RNA binding proteins, to map spliceosome engagement with pre-messenger RNAs in human

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

164 Our data suggest the spliceosome evolved intrinsic mechanisms to reduce the o

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

166 ctor (U2AF) subunits suggest major and minor spliceosome factors required for intron recognition form

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

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

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

170 Stable addition of U2 during early spliceosome formation requires the DEAD-box ATPase PRP5(

171 g the fates of small nuclear (sn)RNAs of the spliceosome from unstable genome-encoded snRNA variants.

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

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

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

175 Here, we disrupt minor spliceosome function in the developing mouse limb by abl

176 Modulation of spliceosome function may thus provide a new therapeutic

177 rapalogs induce cytoxicity by dysregulating spliceosome function via repression of TRIB3, the loss o

178 ng, most cellular processes depend on proper spliceosome function.

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

180 eting molecular alterations (IDH2 mutations, spliceosome gene mutations) or altered signaling pathway

181 formation, including the presence of TP53 or spliceosome gene mutations, a variant allele fraction >1

182 Cancer-associated mutations in the spliceosome gene SF3B1 create a neomorphic protein that

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

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

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

186 Our study reveals how the human spliceosome has co-opted additional proteins to modulate

187 mbined with recent structural studies of the spliceosome have produced a detailed view of the mechani

188 These insights exemplify spliceosome iCLIP as a broadly applicable method for tra

189 Here we used spliceosome iCLIP, which immunoprecipitates SmB along wi

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

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

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

193 rstandable and provide several videos of the spliceosome in action to illustrate the intricate choreo

194 finition, and back-splicing through the same spliceosome in all eukaryotes and should inspire experim

195 to clinical efforts to directly inhibit the spliceosome in patients with refractory leukemias.

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

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

198 of phenotypes in conditional mutants of the spliceosome, including multiple routes to genome instabi

199 These findings lead us to evaluate direct spliceosome inhibition in myeloma, which synergizes with

200 Spliceosome inhibition resulted in the accumulation of h

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

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

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

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

205 are sensitized to inhibition of splicing via spliceosome inhibitors.

206 broad-scale intron retention, suggestive of spliceosome interference, as well as specific alternativ

207 New structures of spliceosome intermediates and associated protein complex

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

209 The spliceosome is a large ribonucleoprotein complex that re

210 After assembly the spliceosome is activated for catalysis by rearrangement

211 The spliceosome is assembled via sequential interactions of

212 Overall, we show that the minor spliceosome is required for limb development via size co

213 the recognition of the adjacent exons by the spliceosome is required for removal of an intron.

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

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

216 machinery controlling the splicing process (spliceosome) is altered in tumours, leading to oncogenic

217 FgPrp4, the only kinase in the spliceosome, is not essential for viability, but is impo

218 icroscopy structure of a human postcatalytic spliceosome just after exon ligation.

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

220 s are excised by the U2-type or the U12-type spliceosomes, large complexes of small nuclear ribonucle

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

222 We here show that the RNA components of the spliceosome likewise influence alternative splicing deci

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

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

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

226 Spliceosome modulation is invisible to RNA or protein ab

227 of PI mechanism, reveal additional modes of spliceosome modulation, and suggest spliceosome targetin

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

229 The spliceosome modulator, E7107, reverses cancer aggressive

230 ulation of the transcriptome, with augmented spliceosome mRNAs and depletion of transcripts involved

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

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

233 Spliceosomes must ensure accurate removal of highly dive

234 nding protein RBM39 as a potential target in spliceosome mutant AML that can be targeted by existing

235 Spliceosome mutations are common in myelodysplastic synd

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

237 Dysregulation of RNA splicing by spliceosome mutations or in cancer genes is increasingly

238 n patients with myeloid malignancies bearing spliceosome mutations relapsed or refractory to standard

239 t solid tumors or leukemia bearing recurrent spliceosome mutations.

240 nd scaffold that recruits and stabilizes the spliceosome near the alternative exon, thus promoting it

241 ions in the genes encoding components of the spliceosome occur frequently in human neoplasms, includi

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

243 e crosstalk and a global impact of the minor spliceosome on major intron splicing.

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

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

246 lish disrupted splicing integrity and "major spliceosome-opathies" as a new mechanism underlying PCHM

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

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

249 on larger protein structures, including the spliceosome, proteasome and RNA polymerase I, as well as

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

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

252 nical implications because mutations in some spliceosome proteins cause microcephaly and/or growth re

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

254 exon ligation, the Saccharomyces cerevisiae spliceosome recognizes the 3'-splice site (3'SS) of prec

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

256 SART3 is a spliceosome recycling factor and nuclear RNA-binding pro

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

258 stably with the 3'-exon after Prp16-mediated spliceosome remodeling.

259 The spliceosome removes introns from messenger RNA precursor

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

261 e introns are spliced by the major and minor spliceosomes, respectively.

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

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

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

265 licate these alleles in the stability of the spliceosome's catalytic core.

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

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

268 ron splicing of a nascent mRNA transcript by spliceosome (SPL) is a hallmark of gene regulation in eu

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

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

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

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

273 modes of spliceosome modulation, and suggest spliceosome targeting as a promising therapeutic strateg

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

275 is not required for recruiting Prp43p to the spliceosome, the 3' end cross-links directly to Prp43p i

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

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

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

279 on splicing parallels functional data on the spliceosome, thus reinforcing the notion that these evol

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

281 g data showing the physical proximity of the spliceosome to Pol II, we surveyed the effect of epigene

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

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

284 the chromatin accessibility, and couples the spliceosome to the chromatin.

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

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

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

288 The spliceosome undergoes dramatic changes in a splicing cyc

289 ors that affect the frequency with which the spliceosome uses cryptic splice sites and identified two

290 Using this model, we show that SF3B1K700E spliceosomes utilize non-canonical sequence variants (at

291 re present in equal stoichiometry within the spliceosome, we found that their relative levels vary by

292 To define BP utilization by SF3B1-mutant spliceosomes, we used an overexpression approach in huma

293 mTOR and disrupted its interaction with the spliceosome, where it participated in rapalog-induced de

294 hed that even core protein components of the spliceosome, which are required for splicing to proceed,

295 of a large ribonucleoprotein machinery, the spliceosome, whose protein core is composed of the Sm ri

296 ngs identify TRIB3 as a key component of the spliceosome, whose repression contributes significantly

297 WBP11 encodes a component of the spliceosome with the ability to activate pre-messenger R

298 trates that SUGP1 loss is a common defect of spliceosomes with disease-causing SF3B1 mutations and, b

299 ily and chemically related to the eukaryotic spliceosome, with potential applications as gene-editing

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