ライフサイエンスコーパス: exon skip

1 berrant mRNAs lacking specific coding exons (exon skipping).

2 ucture and function (e.g., intron retention, exon skipping).

3 inding domain, with alternative splicing and exon skipping.

4 urally mimic those that would be achieved by exon skipping.

5 ring exons 6 and 9 closer, thereby promoting exon skipping.

6 s in the transcriptional elongation rate and exon skipping.

7 d by antisense oligonucleotide (AO)-mediated exon skipping.

8 f a single residue was sufficient to prevent exon skipping.

9 US1 splicing, including intron retention and exon skipping.

10 on in a splice donor site predicted to cause exon skipping.

11 os, delayed neural tube closure, and altered exon skipping.

12 r the observed 100% intron retention without exon skipping.

13 cing, whereas the common SNP A1028A promoted exon skipping.

14 lar mechanism by which this element prevents exon skipping.

15 rease exon inclusion but that CUG-BP1 causes exon skipping.

16 alternative splicing event, skipped exon or exon skipping.

17 tion of antisense oligonucleotides to induce exon skipping.

18 ts, of which 53.5% are IntronR and 13.8% are exon skipping.

19 intron retention (IntronR), and only 8% are exon skipping.

20 m trans-splicing, and circular exons through exon skipping.

21 ced as a result of mRNA frameshift caused by exon skipping.

22 sults in a unique pattern of tissue-specific exon skipping.

23 ucleotides could be used to correct aberrant exon skipping.

24 plicing enhancer (ESE), thereby resulting in exon skipping.

25 e sequences in the dystrophin gene to induce exon skipping.

26 5' splice sites and determined the effect on exon skipping.

27 ition +3 with a purine resulted in increased exon skipping.

28 ingle-nucleotide difference in exon 7 causes exon skipping.

29 icing enhancer (ESE) sequences, resulting in exon skipping.

30 nterfere with exon recognition, resulting in exon skipping.

31 tivity and that two splicing mutations cause exon skipping.

32 ention, and Sudemycins more acute effects on exon skipping.

33 raction with these exonic sequences promotes exon skipping.

34 a recurrent silent third base change, cause exon skipping.

35 nt malignancies to estimate the rate of said exon skipping.

36 insufficient hDBR1 leads to a higher rate of exon skipping.

37 nits with different specificities to promote exon skipping.

38 re disease course than those amenable to any exon skipping.

39 , restoring functional dystrophin protein by exon skipping.

40 nd found that the majority resulted in total exon skipping.

41 tate recognition of splice sites and prevent exon-skipping.

42 n of exons is widespread and correlates with exon skipping, a feature that adds considerably to the r

43 repeatability of platelet RNA expression and exon skipping, a readily measured alternative splicing e

44 echanistic explanation for the variations in exon-skipping activity and restoration of dystrophin pro

45 utation in the dystrophin gene showed strong exon-skipping activity in differentiated mdx mouse myotu

46 olino oligomers (PMOs) with glucose enhances exon-skipping activity in Duchenne muscular dystrophy (D

47 es, higher expression of hDBR1 only affected exon-skipping activity in malignant cells.

48 he RS/P domain and RRM are necessary for the exon-skipping activity, whereas the S domain is importan

49 Exon skipping adds to the unexpected outcomes that must

50 Antisense-oligonucleotide-induced exon skipping allows synthesis of partially functional d

51 as validated by qRT-PCR experiments on eight exon skipping alternative splicing events.

52 wn genes have only a single isoform based on exon-skipping alternative expression.

53 ucted and analyzed a large data set of 1,478 exon-skipping alternative splicing (AS) variants evoluti

54 These novel variants resulted either from exon skipping, alternative usage of splicing signals, or

55 Further, we showed that exon skip and intron retention are predominant splice ev

56 vitro studies revealed that it leads to mRNA exon skipping and ABCA4 protein truncation.

57 da-7 pre-mRNA is differentially spliced, via exon skipping and alternate 5'-splice donor sites, to yi

58 TDP-43 is a nuclear protein involved in exon skipping and alternative splicing.

59 splicing in minigene assays, and resulted in exon skipping and an in-frame deletion of 40 amino acids

60 rized by alternative splicing events such as exon skipping and complete or partial intron inclusion.

61 Exon skipping and cryptic splicing were confirmed by tra

62 had a recessive mutation in PIGQ that led to exon skipping and defective glycophosphatidyl inositol b

63 The mutation leads to exon skipping and deletion of 52-amino acid residues of

64 3' splice site is associated with increased exon skipping and disease.

65 these retroviral-derived exons and result in exon skipping and dysregulated alternative splicing of a

66 ply to other molecular strategies, including exon skipping and gene therapy.

67 The ASOs promote aberrant exon skipping and generation of premature termination co

68 A-to-I editing demonstrate that both the Alu exon skipping and inclusion isoforms encode active enzym

69 mt3 gene knockdown, and change in two types, exon skipping and intron retention, was directly related

70 sence of novel transcriptomic events such as exon skipping and novel indels towards accurate downstre

71 onucleotide conjugate designed to induce Dmd exon skipping and recover dystrophin protein expression

72 dule developmental stage, with activation of exon skipping and repression of intron retention being t

73 merged as front-line molecular therapeutics: exon skipping and stop codon read through.

74 Regulation of exon skipping and tandem alternative 3' splice sites (NA

75 nic enhancers can act as barriers to prevent exon skipping and thereby may play a key role in ensurin

76 2 and FLT3 resulted from complete or partial exon skipping and utilization of cryptic splice sites.

77 dons from variable (V) Igkappa exons promote exon-skipping and synthesis of V domain-less kappa light

78 o repair the primary genetic defect, called 'exon skipping' and 'nonsense codon suppression'.

79 em cells to characterize splicing variation (exon skipping) and its determinants.

80 ecific overexpression of PTB increased alpha-exon skipping, and a reduction in PTB increased alpha-ex

81 hanisms included transcriptional repression, exon skipping, and intron inclusion.

82 utations, one causes a nonsense mutation and exon skipping, and one affects a splice site, were found

83 utic correction of many genetic diseases via exon skipping, and the first AON-based drugs have entere

84 one allele that caused aberrant splicing and exon skipping, and the other allele had an amino acid su

85 long-term treatment with peptide-conjugated exon skipping antisense oligonucleotides (20-week regime

86 irst time the efficiency of the AAV-mediated exon skipping approach in the utrophin/dystrophin double

87 og model of Duchenne muscular dystrophy, the exon-skipping approach recently improved multiple functi

88 f embryonic dystrophin in zebrafish using an exon-skipping approach severely impairs the mobility and

89 or with other diseases that are eligible for exon-skipping approaches requiring whole-body treatment.

90 hat mutations within the repeat that abolish exon skipping are corrected by compensatory mutations in

91 The antisense oligonucleotides used for exon skipping are designed to bypass premature stop codo

92 ture but alternative donor/acceptor site and exon skipping are mainly induced, indicating differentia

93 processing, alternative 5 and 3'ss usage and exon skipping are marked by distinct patterns of ordered

94 In addition to exon skipping, ASO treatment causes intron retention and

95 NM1 protein is also predicted as a result of exon skipping associated with disruption of a consensus

96 mouse provides a favored system for study of exon skipping associated with nonsense mutations.

97 tion factor ETS variant 1 (ETV1) gene showed exon skipping at exon 7, while nudE neurodevelopment pro

98 While in most cases the Alu promotes exon skipping, at one locus the Alu increases exon inclu

99 to do so in an mle(napts) background causes exon skipping because the normal splice donor is occlude

100 e reduction results from gradually increased exon skipping between exons 50 and 219 of titin mRNA.

101 ctivity, LaSSO identified both canonical and exon-skipping branch points.

102 NP M included the ability not only to induce exon skipping but also to promote exon inclusion.

103 SR proteins have also been reported to cause exon skipping, but little is known about the mechanism.

104 ta demonstrate that chimeraplasts can induce exon skipping by altering splice site sequences at the g

105 Exon skipping by ASOs is gaining traction as a therapeut

106 We demonstrate that Rbm20 mediates exon skipping by binding to titin pre-mRNA to repress th

107 ) into protein encoding molecules, or induce exon skipping by disruption of exon splicing enhancers (

108 functional dystrophin protein expression via exon skipping by restoring in-frame transcripts in the m

109 We have now expanded the potential for exon skipping by testing whether an internal, in-frame t

110 ion pressure on alternatively spliced single-exon skips, by calculating the fraction that are an exac

111 AS in BRCA1, we show here that inappropriate exon skipping can be reproduced in vitro, and results fr

112 Exon skips cause loss of inversin protein motifs, includ

113 DE9) expressed by cancer cells with MSI, via exon skipping caused by somatic deletions in the T(17) i

114 me deletions relevant to on-going or planned exon skipping clinical trials for Duchenne muscular dyst

115 to improve and better predict the outcome of exon skipping clinical trials.

116 uman muscle disease and showed that multiple exon skipping could be induced in RNA that encodes a mut

117 es, the upstream intron was removed, so that exon skipping could not occur.

118 ellular trafficking correspond well with the exon-skipping data, with higher activity in myotubes tha

119 rtion, small in-frame deletions and a larger exon-skipping deletion.

120 ut mice, we now show that SR protein-induced exon skipping depends on their prevalent actions on a fl

121 chenne muscular dystrophy, the rationale for exon skipping derived from observations in patients with

122 oximately 80% cis), whereas species-specific exon skipping differences are driven by both cis- and tr

123 lection because gene splicing analysis shows exon skipping due to loss of the ESE.

124 ory circuit of sense-antisense pairs and the exon skipping during alternative splicing, through inter

125 Exon skipping (ES) is reported to be the most common alt

126 We present an exon skipping event in HDAC7, which is a candidate gene

127 eptides with one single intron event and one exon skipping event were identified.

128 Particularly, exon-skipping event in Enhancer of Zeste Homologue 2 (EZ

129 This exon-skipping event is associated with a mutation at the

130 ive complex PRC2, and the down-regulation of exon-skipping event may lead to the regain of functional

131 p a new target function for AS prediction in exon skipping events and show it significantly improves

132 al features due to ES events, and studies of exon skipping events associated with mutations and methy

133 GGAC identified by CoSREM may play a role in exon skipping events in several tumor samples.

134 Several exon skipping events were also highly repeatable, sugges

135 On the other hand, exon skipping events were rare in coding regions (1%) bu

136 -PCR validation rate of 86% for differential exon skipping events with a MATS FDR of <10%.

137 mily within exons 3 and 4 contributes to the exon skipping events, although the most commonly observe

138 nges in pre-mRNA splicing with prevalence of exon skipping events.

139 ities to identify therapeutically targetable exon skipping events.

140 ort splice variants of KV10.1 resulting from exon-skipping events (E65 and E70) in human brain and ca

141 lgorithm also aids in the discovery of micro-exon-skipping events and cross-species micro-exon conser

142 In addition, we observe exon-skipping events in c-MET, which are attributable to

143 Exon-skipping events increased in cells deficient for th

144 Interestingly, 29 exon-skipping events induced by treatment were identifie

145 iring by determining the number of incorrect exon-skipping events made from constitutively spliced pr

146 ations of tumor suppressor genes often cause exon-skipping events that truncate proteins just like cl

147 of all annotated introns, hundreds of novel exon-skipping events, and thousands of novel introns.

148 events, but also pinpointed novel, but rare, exon-skipping events, which may reflect aberrantly splic

149 rute-force algorithms to detect all possible exon-skipping events, which were widespread but rare com

150 nts with Becker MD and mdx mice subjected to exon skipping exhibited inhibited dystrophin degradation

151 suppressor genes, including whole or partial exon skipping, exonification of intronic sequence, loss

152 t internally deleted dystrophins produced by exon skipping for different mutations; more insight woul

153 However, antisense oligonucleotide-mediated exon skipping for DMD still faces major hurdles such as

154 ophies, with an emphasis on gene therapy and exon skipping for DMD.

155 e with an exon 5-targeted ASO-induced robust exon skipping for more than a year, improved motor coord

156 g the mutations in cell lines to demonstrate exon skipping from the deletion mutation and the activat

157 ystems but for which no previous examples of exon-skipping had been demonstrated.

158 In particular, antisense-mediated exon skipping has shown encouraging results and holds pr

159 Indeed, antisense oligonucleotide-based exon skipping has shown promise for RDEB.

160 As such, chimeraplast-mediated exon skipping has the potential to be used to transform

161 ns, antisense oligonucleotide (AON)-mediated exon skipping has the potential to restore a functional

162 uction by antisense oligonucleotides, termed exon-skipping, has been reported for the mdx mouse and i

163 specificity was observed, with differential exon skipping in 5% of genes otherwise coexpressed in bo

164 verexpression of RNPS1 in HeLa cells induced exon skipping in a model beta-globin pre-mRNA and a huma

165 nes, were shown to cause intron retention or exon skipping in an allele-specific manner, with approxi

166 enous CD44 gene revealed that CARM1 promotes exon skipping in an enzyme-dependent manner.

167 a critical regulator of both signal-induced exon skipping in CD45 and global alternative-transcript

168 ASOs also induced exon skipping in cell lines derived from patients with C

169 Given the success of exon skipping in clinical trials to treat genetic diseas

170 F3-affected AS events, with a preference for exon skipping in genes involved with cell mitosis.

171 in widespread intron retention and cassette exon skipping in leukemic cells regardless of Srsf2 geno

172 tion was decreased due to the high levels of exon skipping in non-SM cell lines.

173 splice site recognition and contributing to exon skipping in nonneural cells.

174 t of a deep intronic/branch-site mutation on exon skipping in PTEN but also found that different spli

175 Mutant U2AF1 promotes enhanced splicing and exon skipping in reporter assays in vitro.

176 transgenes whose expression is activated by exon skipping in response to a specific protein inducer.

177 licing silencer in CD45 exon 4 confers basal exon skipping in resting T cells through the activity of

178 Multimerisation of the URE caused enhanced exon skipping in SM and various non-SM cells.

179 However, four exons are subject to exon skipping in some transcripts, giving rise to five s

180 ty of hnRNP L and confers activation-induced exon skipping in T cells via previously unknown mechanis

181 This element (In100) can facilitate exon skipping in the context of competing 3' or 5' splic

182 ted in a reduction of dystrophin protein and exon skipping in the diaphragm.

183 avenous oligonucleotide (morpholino)-induced exon skipping in the DMD dog model.

184 ong isoforms of Cask and Madd, and mimicking exon skipping in these transcripts through antisense oli

185 This, together with exon skipping in two noncontiguous regions, favors aberr

186 have previously been found to correlate with exon-skipping in both lymphocytes and tumors from patien

187 ession by antisense oligonucleotide-mediated exon-skipping in mdx mice and (2) stable restoration of

188 switching and differential exon usage (i.e., exon-skipping), in addition to its effects on gene expre

189 1 were shown to be critical determinants for exon skipping, indicating that LINE1 acts as efficient m

190 Therapeutic restoration of dystrophin by exon skipping induced widespread shifts in protein and m

191 rsity can be placed into four major classes: exon skipping, intron retention, alternative 5' splice s

192 ere discovered, which were generated through exon skipping, intron retention, and alternative usage o

193 Exon skipping is a common result of splice mutations and

194 , antisense oligonucleotides (ASOs) mediated exon skipping is a promising therapeutic approach.

195 Exon skipping is a promising therapeutic strategy for Du

196 to improve this therapeutic approach to DMD.Exon skipping is a strategy for the treatment of Duchenn

197 Exon skipping is a widespread phenomenon occurring acros

198 Antisense oligonucleotide-mediated exon skipping is able to correct out-of-frame mutations

199 This study, by demonstrating that targeted exon skipping is able to rescue ciliary protein composit

200 Exon skipping is also more likely to occur when exons ar

201 Exon skipping is capable of correcting frameshift and no

202 Exon skipping is considered a principal mechanism by whi

203 Exon skipping is currently being tested in humans with d

204 ably, the effect of the nonsense mutation on exon skipping is incomplete.

205 Antisense-mediated exon skipping is one of the most promising approaches fo

206 gulatory role in the pathway leading to male-exon skipping is sans-fille (snf), a protein component o

207 Although SMN2 exon skipping is the principal contributor to SMA severi

208 ister cell the BDU neuron expresses only the exon-skipped isoform.

209 analysis confirms that this mutation causes exon skipping, leading to an out-of-frame fusion of BRCA

210 The mutation leads to exon skipping, leaving the coding region in frame.

211 on in MYPT1 and switch to the 3' alternative exon skipped/leucine zipper positive MYPT1 isoform.

212 bi-specific CPP-PMOs demonstrated comparable exon skipping levels for both pre-mRNA targets when comp

213 ells, illustrating that SR protein-dependent exon skipping may constitute a key strategy for synergis

214 ve to neutral polymorphisms, indicating that exon skipping may play a prominent role in aberrant gene

215 We also described an exon-skipping mechanism for CARD11 dominant-negative act

216 transcript, indicating that it arises by an exon-skipping mechanism of alternative splicing.

217 e recurrent in lung adenocarcinoma and cause exon skipping (METDelta14).

218 tectable binding and signal transduction for exon-skipping mutated constructs.

219 We now report characterization of an exon-skipping mutation (IVS3+5G-->A at the intron 3 spli

220 e pathogenic allele in exon 41, including an exon-skipping mutation that induced an in-frame deletion

221 Patients with COL3A1 exon skipping mutations had higher plasma intercellular

222 Exon skipping mutations of the Hypocretin/Orexin-recepto

223 Functional analysis of previously-described exon-skipping mutations and of the E54K substitution wer

224 ced urticaria and immune dysregulation PLCG2 exon-skipping mutations resulting in protein products wi

225 Finally, we describe two disease-related exon-skipping mutations that create hnRNP A1 binding sit

226 pecific alternative splicing events, such as exon skipping,mutually exclusive exons, alternative 3' a

227 usively intron retention, in contrast to the exon skipping observed in vertebrates.

228 The two-exon skip occurred in transcripts in which intron 5 was

229 mdx mice with morpholino oligomers to induce exon skipping of dystrophin exon 23 (that results in fun

230 rfan syndrome (MFS) patient induces in-frame exon skipping of FBN1 exon 51.

231 Duchenne muscular dystrophy, we propose that exon skipping of FcepsilonRIbeta is a potential approach

232 2a was common in all cardiac muscle samples, exon skipping of Myocd exon 10a was a rare event in both

233 and disrupted the developmentally regulated exon skipping of Ndel1 mRNA, which is bound by MBNL1 and

234 nsistent with the formation of GABA(B)R1c by exon skipping of one sushi domain module.

235 uch as antisense oligonucleotides, to induce exon skipping of specific mutations or drugs developed t

236 ivo using antisense oligonucleotide-mediated exon skipping of the beta-subunit of the high-affinity I

237 usly characterized SRSF1 (SF2/ASF)-dependent exon skipping of the CaMKIIdelta gene during heart remod

238 splicing of ClC-1 and that antisense-induced exon skipping offers a powerful method for correcting al

239 Here using exon skipping oligonucleotides we predominantly restored

240 t splicing resulting in either mis-splicing, exon skipping or inclusion of alternative exons, consist

241 ding near the 3' splice site promoted either exon skipping or inclusion.

242 ed across species that are generated through exon skipping or insertion that encodes proteins contain

243 t some single-guide RNAs (sgRNAs) can induce exon skipping or large genomic deletions that delete exo

244 in expression to diseased cells is known as 'exon skipping' or splice-modulation, whereby antisense o

245 influencing regulatory elements, leading to exon skipping, or by creating a new cryptic splice site.

246 ic matrices and that accurately predicts the exon-skipping phenotypes of deleterious point mutations.

247 oration through micro-dystrophin delivery or exon skipping, preclinical models have shown that incomp

248 hich we built the winning model of the CAGI5 exon skipping prediction challenge.

249 Drug-induced exon skipping preferentially affects shorter alternative

250 Two drugs developed for exon skipping, PRO051 and AVI-4658, result in the exclus

251 nd the nuclear exosome in the degradation of exon-skipped products is also observed for three other g

252 splicing modulator-induced intron-retention/exon-skipping profile, which correlates with the differe

253 ligonucleotides) in DMD pre-mRNA can lead to exon skipping, restoration of the open reading frame, an

254 AON-induced exon skipping resulted in specific Alk4 down-regulation,

255 further confirmed that all 3 variants caused exon skipping resulting in frameshifts that lead to prem

256 ssociated with increased polyadenylation and exon skipping, resulting from the actions of ELL2 transc

257 ed a novel computational method, graph-based exon-skipping scanner (GESS), for de novo detection of s

258 of several alternative methods shows that an exon-skipping score based on neighboring junctions best

259 Mutations at splice junctions often cause exon skipping, short deletions, or insertions in the mat

260 reading-frame in both the exon-inclusion and exon-skip splice forms.

261 e combined to predict effects of variants on exon skipping, splice site choice, splicing efficiency,

262 ence conferring competitive advantage to the exon-skipping splicing event (E8-E10).

263 turn confers a competitive advantage to the exon-skipping splicing pattern.

264 cided with the switch from exon inclusion to exon skipping, suggesting that loss of TIA and SR enhanc

265 erved in patients with mutations amenable to exon skipping than in those not amenable.

266 t a novel mechanism for altered splicing and exon skipping that is independent of traditional introni

267 This causes exon skipping, the in-frame deletion of 46 amino acids f

268 o all three families and was shown to induce exon skipping; the other mutations were frameshift mutat

269 Exon-skipping therapies aim to convert Duchenne muscular

270 neuropathy, and promising gene transfer and exon-skipping therapies for muscular dystrophy are among

271 ame deletions and insertions are targeted by exon-skipping therapies.

272 mdx mice, combined dystrophin and myostatin exon skipping therapy greatly improved DMD pathology, co

273 s as well as the biodistribution of ASOs for exon skipping therapy.

274 oligomers (PMOs) has shown great promise for exon-skipping therapy of Duchenne Muscular Dystrophy (DM

275 ing adeno-associated virus (AAV)-U7-mediated exon-skipping therapy was shown to decrease drastically

276 tant implications for the development of DMD exon-skipping therapy.

277 Although very effective in correcting exon skipping, they also induced retention of the short

278 A switch from cTNT exon skipping to inclusion tightly correlated with induc

279 antisense oligonucleotide (ASO) that induces exon skipping to restore the open reading frame.

280 ne, read-through of translation stop codons, exon skipping to restore the reading frame and increased

281 ts, including nonsense codon suppressors and exon skipping, to gene therapy using viral and nonviral

282 % restoration of wt dystrophin levels, using exon-skipping, together with increased utrophin levels r

283 These include ORF assignment of exon skipped transcript, studies of lost protein functio

284 These exon-skipping transcripts are therefore unlikely to be f

285 The pervasive exon-skipping transcripts were stochastic, did not incre

286 strophy with deletions relevant for on-going exon skipping trials in Duchenne muscular dystrophy.

287 srupts normal MLH1 mRNA processing, and that exon skipping underlies pathogenesis in these HNPCC fami

288 Exon skipping uses antisense oligonucleotides (ASOs) to

289 Exon skipping uses antisense oligonucleotides as a treat

290 and dystrophin production can be achieved by exon skipping using antisense oligonucleotides targeted

291 4-8) corresponding to LBD to produce namely exon-skipping variants.

292 The average splicing rate by exon skipping was approximately 0.24% in wild type and a

293 Exon skipping was confirmed by reverse transcription-pol

294 Exon skipping was the major splicing event observed.

295 To prevent exon-skipping, we have targeted an intronic repressor, E

296 ms for internal alternative cis-splicing and exon skipping were active in multiple life cycle stages

297 Both exon inclusion and exon skipping were found to post-transcriptionally regul

298 ing enhancer (ESE), for example, could cause exon skipping which would result in the exclusion of an

299 ncated reading frame upstream of the IRES by exon skipping, which led to synthesis of a functional N-

300 sma cells, enhanced both polyadenylation and exon skipping with the gene encoding the immunoglobulin