ライフサイエンスコーパス: splice site

1 ces and their stoichiometry determine the 3'-splice site.

2 uces multiple circRNAs sharing the same back-splice site.

3 Our data also do not support it being a splice site.

4 s: a 5' splice site, a branch site, and a 3' splice site.

5 side before its release from the pre-mRNA 5' splice site.

6 lic attack of the branch adenosine at the 5' splice site.

7 49T > G, predicted to generate a novel donor splice site.

8 mutated SF3B1 residues contact the pre-mRNA splice site.

9 the spliceosomal U1 snRNP to a suboptimal 5' splice site.

10 e forms a hairpin that weakly tethers the 5' splice site.

11 n of nucleotide 'C' at position -3 of the 3' splice site.

12 Each transposon carries one splice site.

13 the recognition of weak Py-tracts at the 3' splice site.

14 ic splice site at the expense of a canonical splice site.

15 ractions with cis elements that overlap a 5' splice site.

16 d by the structural context of the available splice sites.

17 egulated process dependent on sequences near splice sites.

18 ate variants in coding regions and essential splice sites.

19 ncing confirmed backsplicing using canonical splice sites.

20 ancy and more likely to contain nonconsensus splice sites.

21 exonic cores, even after excluding canonical splice sites.

22 (Py) signals preceding the major class of 3' splice sites.

23 xonic sequences and are spliced at canonical splice sites.

24 regulatory signals, including a role for RNA splice sites.

25 ome must distinguish optimal from suboptimal splice sites.

26 a minigene transcript carrying prototypical splice sites.

27 a distinctly asymmetric profile around known splice sites.

28 l crosslinking around branchpoints (BPs) and splice sites.

29 outcome more dependent on the optimality of splice sites.

30 ssociated genes at noncanonical positions in splice sites.

31 confirmed that SF3B1 mutants use aberrant 3' splice sites.

32 n-1 and examined how alternative splicing at splice site #2 (SS2) regulates the complex.

33 we identified 14 different novel variants (2 splice site, 2 frameshift and 10 missense changes) in GN

34 ces cerevisiae spliceosome recognizes the 3'-splice site (3'SS) of precursor messenger RNA (pre-mRNA)

35 SF3B1 mutations induce use of cryptic 3' splice sites (3'ss), and these splicing errors contribut

36 3 B1 (SF3B1) result in selection of novel 3' splice sites (3'SS), but precise molecular mechanisms of

37 aberrant pre-mRNA splicing using cryptic 3' splice sites (3'SSs), but the mechanism of their selecti

38 to pre-mRNA guided by specific sequences (5' splice site, 3' splice site, and branchpoint).

39 The selection of 3 splice sites (3ss) is an essential early step in mammali

40 native splicing of presynaptic neurexin-1 at splice site 4 (SS4) dramatically enhanced postsynaptic N

41 NPs) bound to the precursor messenger RNA 5' splice site (5'SS) and branch point sequence, associates

42 Transfer of the 5' splice site (5'SS) from U1 to U6 snRNA triggers unwindin

43 er N1 (ISS-N1), located downstream of the 5' splice site (5'ss) of exon 7.

44 e first catalytic step of splicing at the 5' splice site (5'ss).

45 shorten the minimal distance between the 5' splice-site (5'SS) and branchpoint.

46 roligin splice site B, little is known about splice site A.

47 intron contains three obligate signals: a 5' splice site, a branch site, and a 3' splice site.

48 IVS2-654)-globin pre-mRNA such as cryptic 3' splice site, aberrant 5' splice site, cryptic branch poi

49 om lymphoblastoid cells demonstrated partial splice site abolition and the creation of an abnormal is

50 fy RNA metabolic rates at donor and acceptor splice sites across the human genome.

51 r results provide a mechanism for exon 16 3' splice site activation in which a coordinated effort amo

52 tification of global locations of endogenous splice-site activation by lariat sequencing confirms the

53 Our findings suggest that cryptic splice-site activation is more common than previously th

54 Splice-site activation was predicted for 129 (28%) of th

55 The 3'-splice site AG dinucleotide is recognized through non-Wa

56 n-trapping assays with constructs containing splice site alleles revealed errors in splicing.

57 on, mutually exclusive exons, alternative 5' splice site, alternative 3' splice site and retained int

58 We provide a formal definition of splice site ambiguity due to the genomic sequence by int

59 Splice site analysis of rs12252_C was performed using PI

60 o acid residues, leading to perturbed normal splice site and exon recognition.

61 ibit a distinctive molecular profile for the splice site and protein interactomes.

62 , alternative 5' splice site, alternative 3' splice site and retained intron.

63 sequence variation, including those in core splice site and splicing motifs.

64 through non-Watson-Crick pairing with the 5' splice site and the branch-point adenosine.

65 hich included 16 patients, we identified one splice site and three heterozygous missense mutations in

66 ly assess spliceogenicity outside the native splice site and thus the disease-causing potential of va

67 RNA polymerase II (Pol II) at promoters, 5' splice sites and active enhancers, and are processed by

68 chromatin-bound lncRNAs are enriched with 5' splice sites and depleted of 3' splice sites, and exhibi

69 ion that leads to splicing between HIV donor splice sites and downstream human exons.

70 ency with which the spliceosome uses cryptic splice sites and identified two alleles in core spliceos

71 Moreover, when both splice sites and poly(A) signals were mutated, polyadeny

72 sortium, to investigate selection around the splice sites and quantify the contribution of splicing m

73 structural elements near the alternative 5' splice sites and show that splice site choice is signifi

74 t recognition leading to usage of cryptic 3'-splice sites and subsequent aberrant junctions.

75 vely, the strong nucleosome positioning over splice sites and surrounding putative transcription fact

76 cancer cells is regulated by competition for splice sites and that combinations of splicing factors i

77 , RBMXL2 represses the selection of aberrant splice sites and the insertion of cryptic and premature

78 tely sensitive to the sequence context of 3' splice sites and to small structural differences between

79 tial correlation of CAGE clusters with donor splice sites and with poly(A) sites.

80 nic germline variants in SCAF4 including two splice-site and seven truncating variants, all residing

81 g sequences and generate missense, nonsense, splice site, and 5' and 3' untranslated region mutations

82 c acid-binding domain, recognition of the 3' splice site, and alternative splicing of many mRNAs.

83 ed by specific sequences (5' splice site, 3' splice site, and branchpoint).

84 de novo CNOT1 variants, including missense, splice site, and nonsense variants, who present with a c

85 athogenic DLL1 variants (nonsense, missense, splice site, and one whole gene deletion).

86 th achromatopsia include missense, nonsense, splice site, and single-nucleotide deletion or duplicati

87 ogether to identify the 5 splice site, the 3 splice site, and the branchsite (BS) of nascent pre-mRNA

88 ched with 5' splice sites and depleted of 3' splice sites, and exhibit high levels of U1 snRNA bindin

89 r from native genes in GC-content, number of splice sites, and gene expression.

90 position and nature of nucleotides flanking splice sites, and on structural interactions between uns

91 onation of alternative promoters, enhancers, splice sites, and termination signals.

92 CA-RNA are within 50 nucleotides of 5' or 3' splice sites, and the vast majority of exons harboring m

93 terious ARMC9 variants (stop-gain, missense, splice-site, and single-exon deletion) in 11 individuals

94 ing, the mechanisms that drive the choice of splice site are poorly understood.

95 iency, and introns with alternative 5' or 3' splice sites are less efficiently spliced.

96 When splice sites are mutated, as in many hereditary diseases

97 other variants that may create or eliminate splice sites are often clinically classified as variants

98 uctionist approach focused on how individual splice sites are recognized.

99 epithelial transition (MET) near the exon 14 splice sites are recurrent in lung adenocarcinoma and ca

100 the catalytic stage of splicing, suboptimal splice sites are repressed by the DEAH-box ATPases Prp16

101 How cognate (functional) splice sites are selectively used in lieu of these crypt

102 uts that determine the efficiency with which splice sites are utilized remain poorly defined.

103 83% of SDVs are located outside of canonical splice sites, are distributed evenly across distinct exo

104 a systematic analysis on the conservation of splice-sites as a measure of gene-structure based on mul

105 one of these is the activation of a cryptic splice site at the expense of a canonical splice site.

106 stronger Py-tracts, as required to define 3' splice sites at early stages of spliceosome assembly.

107 In contrast to the well-studied neuroligin splice site B, little is known about splice site A.

108 The U1 snRNA mutations occur in the 5' splice-site binding region, and snRNA-mutant tumours hav

109 wn of popdc3 in zebrafish, using 2 different splice-site blocking morpholinos, resulted in larvae wit

110 Recognition of highly degenerate mammalian splice sites by the core spliceosomal machinery is regul

111 ; p.Pro166His and c.1229A>G; p.Asp410Gly), 1 splice site (c.1282A>C p.Ser428Arg), 1 frameshift (c.470

112 , c.2352_2353insC (p.Arg785Glnfs( *)23), and splice-site, c.4549-1G>A, mutations were identified.

113 in SMOC2 promotes the utilization of cryptic splice sites, causing its incorporation into transcripts

114 ded 10 missense mutations, 1 deletion, and 3 splice-site CD37 mutations.

115 nopore reads, we demonstrate differential 3' splice site changes associated with SF3B1 mutation, agre

116 osition in determining in vivo mechanisms of splice site choice in LMNA.

117 While splice site choice is in part defined by sequence comple

118 he alternative 5' splice sites and show that splice site choice is significantly influenced by the st

119 ne expression, while allowing flexibility in splice site choice with the nonribosomal protein transcr

120 redict effects of variants on exon skipping, splice site choice, splicing efficiency, and pathogenici

121 tribute to splicing regulation by modulating splice site choice.

122 ble window sizes and options to annotate the splice sites closest to the variants and to consider the

123 these exon-creating mutations suggests that splice sites created by non-coding mutations interact wi

124 such as cryptic 3' splice site, aberrant 5' splice site, cryptic branch point and an exonic splicing

125 and simple library prep and high resolution splice site detection.

126 suggesting SFPS might be involved in the 3' splice site determination.

127 Variants affecting essential splice-site dinucleotides inhibit splicing, whereas the

128 nd stabilize a conformation competent for 3'-splice site docking, thereby promoting exon ligation.

129 The mechanism of splice site exchange within the RNA active site during c

130 One 9-bp duplication and one splice-site, five missense, and two nonsense variants in

131 s process involves the use of alternative 3' splice sites for the internal intron, the resulting alte

132 How the spliceosome distinguishes authentic splice sites from cryptic splice sites is poorly underst

133 tion, we here identified that the accidental splicing site generates a defective transcript variant w

134 IFITM3 rs12252_C, a putative alternate splice site, has been associated with influenza severity

135 Non-coding mutations can create splice sites, however the true extent of how such somati

136 ions with obvious exonic coding or canonical splice site impact.

137 on (c.1909+22G>A), which activates a cryptic splice site in a tissue and stage of development-specifi

138 nerated by alternative splicing at a cryptic splice site in exon 7.

139 rnal deletion due to activation of a cryptic splice site in exon 9 of the gene (c.1090_1129del; p.Val

140 in patients revealed activation of a cryptic splice site in intron 4 resulting in a frame shift and a

141 and (ii) RPS3 binding activates a poison 5'-splice site in its pre-mRNA that leads to a frame shift

142 e, homozygous c.191A > G variant affecting a splice site in SLC7A6OS.

143 termed VEGFAxxxb that utilise an alternative splice site in the final exon have been widely reported,

144 b (resulting from alternative usage of a 3' splice site in the terminal exon) is protective for kidn

145 ce of the latter correlation, we mutated the splice sites in an affected intron to consensus and foun

146 initio is impossible in the vast majority of splice sites in annotated circRNAs and linear transcript

147 determined that two competing alternative 5' splice sites in exon 12 yield Esrp1 isoforms with differ

148 midine (Py) signals of the major class of 3' splice sites in human gene transcripts remains incomplet

149 ccur in 88.64% and 78.64% of annotated human splice sites in linear and circRNA junctions, respective

150 m(6)A near splice sites in nascent pre-mRNA modulates hnRNPG bindin

151 The presence of canonical splice sites in the mtRNA introns and of core components

152 Thus, identifying splicing sites in DNA/RNA sequences is significant for b

153 a2 expression using translation blocking and splice-site interfering morpholinos.

154 64 genes where transposons introduce cryptic splice sites into the nascent transcript and thereby sig

155 novel elements of RNA processing-alternative splice sites, introns, and cleavage sites-which are ofte

156 situated between the branch point and the 3' splice site is crucial for inclusion.

157 Identification of splice sites is critical to gene annotation and to deter

158 nguishes authentic splice sites from cryptic splice sites is poorly understood.

159 erization or cleavage of HAC1(u) mRNA at the splice site junctions.

160 The del12 mutation activates a cryptic splice site, leading to a frameshift mutation and a prem

161 els of the R47H variant introduced a cryptic splice site, leading to nonsense mediated decay.

162 Preferential selection of the mutant splice site likely reflects its positioning adjacent to

163 orates a sliding window algorithm to predict splice site loss or gain for any variant that overlaps a

164 tify a recurrent homozygous c.408+1G>A donor splice site loss-of-function mutation in DDRGK domain co

165 at retained introns tend to have a weaker 5' splice site, more Gs in their poly-pyrimidine tract and

166 BCB11 mutations - Glu297Gly (x3) and a donor splice site mutation (intron 19).

167 re-attributes the phenotypes to an essential splice site mutation affecting adgra2 (gpr124) splicing

168 verified by Sanger sequencing, identified a splice site mutation c.212 + 1 G > T in the SNX10 gene e

169 ompound heterozygous for p.Gly131Glu and the splice site mutation c.240-1G>C, previously reported in

170 enital adrenal hyperplasia, and an essential splice site mutation in a proband with partial lipodystr

171 A splice site mutation in the canine pyruvate dehydrogenas

172 al pattern despite the presence of the donor splice site mutation, likely due to the action of a puta

173 identified a subject harboring a homozygous splice-site mutation (c.2031-2A>C) in MPO.

174 A conserved splice-site mutation in 1 copy of the suppressor of fuse

175 Patients are homozygous for a splice-site mutation in ABCC9 (c.1320 + 1 G > A), which

176 hole-exome sequencing confirmed a homozygous splice-site mutation in SMARCD2.

177 We found that a splice-site mutation in the component of the transcripti

178 , Reln(CTRdel), carries a chemically induced splice-site mutation that truncates the C-terminal regio

179 hat exclusively express MPc by inserting the splice-site mutation.

180 single-guide RNA (sgRNA) can correct an A>G splice-site mutation.

181 in, frame shift, initiation codon (INIT) and splice site mutations (n = 930, OR = 1.3, P = 1.5xE-5).

182 ere compound heterozygous for frameshift and splice site mutations leading to reduced, but not absent

183 proteins to the NP1 open reading frame, and splice site mutations that prevented their expression in

184 No nonsense or essential splice site mutations were found in 2,479 controls, whil

185 higher risk of malignancy, compared to leaky splice site mutations.

186 third family were compound heterozygous for splice-site mutations c.700+1G>T and c.4002+1G>A.

187 Two splice-site mutations were identified, including homozyg

188 ssion in a subset of NSCLC cases, as well as splicing site mutations facilitating exon 16 skipping an

189 Among them, three are splicing site mutations, four are nonsense mutations, se

190 teins, gene somatic changes of short indels, splice site, nonsense, or missense mutations were detect

191 ort RNA duplex is established between the 5' splice site of a pre-mRNA and the 5' end of the U1 snRNA

192 ar positions within and around the consensus splice site of greater functional relevance.

193 tely identified 168 of 180 (93.3%) canonical splice sites of five genes.

194 AG>AT) containing a point mutation in the 5' splicing site of exon 3a (3aAG > AT); and (iii) Ccalpha6

195 berrantly select nearby pseudo- or "cryptic" splice sites, often resulting in nonfunctional protein.

196 tified a homozygous mutation at an essential splice site on USP18.

197 sertions of Alu retrotransposons can disrupt splice sites or bind splicing regulators.

198 notype due to leakiness (e.g. use of cryptic splice sites or downstream AUGs).

199 ame E12 skipping through the modification of splice sites or regulatory elements and, consequently, l

200 circRNA formation by altering the canonical splicing site or the reverse complementary sequence matc

201 Patients with intronic, splice site, or nonsense DMD mutations, with available m

202 lead to a premature stop, disrupt canonical splice sites, or lead to insertions/deletions that shift

203 m a bridging structure that enforces correct splice site pairing.

204 sequence, secondary RNA structure and linear splice site position in determining in vivo mechanisms o

205 among RNA sequence, secondary structure and splice site position.

206 %-40% of pathogenic variants in noncanonical splice site positions are missing from public databases.

207 can and extends its functionality to provide splice site predictions using a maximum entropy model.

208 Private exons often arise from cryptic splice sites providing an important clue for variant pri

209 ding splicing of variable exons that contain splice site-proximal G-quadruplexes.

210 U1 snRNP plays a critical role in 5'-splice site recognition and is a frequent target of alte

211 e the molecular mechanism and dynamics of 3' splice site recognition by U2AF65 and the role of U2AF35

212 The mechanism of 3'-splice site recognition during exon ligation has remaine

213 Genes involved in 3'-splice site recognition during mRNA splicing constitute

214 ely phenocopying the alterations in exon and splice site recognition induced by hotspot mutations or

215 To understand how exon and intron length and splice site recognition mode impact splicing, we measure

216 f several of these mutations on splicing and splice site recognition, functional connections linking

217 r a branch point-based scanning model for 3' splice site recognition.

218 d SR proteins, which then promotes efficient splice-site recognition and subsequent spliceosome assem

219 elements that control exon definition and/or splice-site recognition.

220 s thaliana) Splicing Factor1, involved in 3' splicing site recognition.

221 racterizes these cancers and did not vary by splice-site region and mutation type of the MET exon 14

222 nucleotide polymorphisms (SNPs), coding and splice-site regions of 10 AMD-(related) genes (ARMS2, C3

223 CFTR gene, generating new acceptor and donor splice sites respectively.

224 orphisms (SNPs) within and outside essential splice sites, respectively, suggesting their regulation

225 utation activates an internal alternative 5' splice site, resulting in formation of the disease-causi

226 C>T (3849+10 kb C>T), which creates a new 5' splice site, resulting in splicing to a cryptic exon wit

227 This mutation creates a new and preferred 3' splice site, results in a 10 nt insertion in mRNA, shift

228 the conformational dynamics of U2AF2 and its splice site RNA complexes.

229 served catalytic triad is protonated upon 5'-splice-site scission, promoting a reversible structural

230 length together with secondary structure and splice site score.

231 2 auxiliary factor 1 (U2AF1) functions in 3'-splice site selection during pre-mRNA processing.

232 Research into the problem of splice site selection has followed a reductionist approa

233 Together, these results demonstrate that 5' splice site selection in LMNA is determined by an intric

234 The underlying mechanism for this 5' splice site selection is unknown.

235 the affected factors, U2AF1, is involved in splice site selection, and the most common change, S34F,

236 h U2AF2 that is primarily responsible for 3' splice site selection.

237 nd disruption to gene expression by aberrant splice site selection.

238 16 that targets SRSF1, it did not affect the splice site shifting activity of SRSF1.

239 ctor U2AF2 recognizes a polypyrimidine-tract splice-site signal and initiates spliceosome assembly.

240 f molecular recognition for a major class of splice site signals.

241 th de novo KCNN2 variants (one nonsense, one splice site, six missense variants and one in-frame dele

242 rs72613567, a splice-site SNP in high linkage with rs6834314 (r(2) = 0

243 Using splice site-specific antisense morpholino oligos, we inh

244 iceosome complexes revealed mechanisms of 5'-splice site (ss) recognition, branching, and intron rele

245 The spliceosome must identify the correct splice sites (SS) and branchsite (BS) used during splici

246 ic analysis of proteins interacting with the splice sites (SSs), we have identified many previously u

247 e nucleotide polymorphisms influencing known splice site strength were also associated with environme

248 d conserved properties, including length and splice site strengths, of retained introns and skipped e

249 erts a GG to an AG, generates a consensus 3' splice site that shifts the reading frame, and creates a

250 scover alternative conformations at critical splice sites that influence the ratio of transcript isof

251 tations interact with pre-existing potential splice sites that originally lacked a suitable splicing

252 modified version, we also discovered a novel splicing site the original mutation, TP53 c.359A>G, may

253 spliceosome work together to identify the 5 splice site, the 3 splice site, and the branchsite (BS)

254 ajor splice donors (MSDs) can activate novel splice sites to produce HIV-1 transcripts, and cells wit

255 inants of the differential sensitivity of 3' splice sites to these drugs.

256 io of circular reads to linear reads in back-splicing sites to study spatial and temporal regulation

257 pable of forming RNA:RNA duplexes that bring splice sites together for backsplicing are known to faci

258 re neural networks scoring exon, intron, and splice sites, trained on distinct large-scale genomics d

259 o novel variants include nine missense, four splice site, two non-sense, one insertion and six gross

260 terodimer is bound to a strong, uridine-rich splice site, U2AF2 switches to a lower FRET value charac

261 s, we identified 244,246 coding-sequence and splice-site ultra-rare variants (URVs) that were unique

262 Splice site usage has been mapped exhaustively across di

263 ce of chromatin factors on cotranscriptional splice site usage remains unclear.

264 equence of the pre-mRNA is a predictor of 5' splice site usage, with the distal position favored over

265 ster cotranscriptional splicing and proximal splice site use, indicating regulatory significance for

266 heterogeneity in RNA conformation regulates splice-site use and viral gene expression.

267 shift (p.[A1048fs*13], p.[L849Afs*3]), and a splice site variant (c.761 + 2T>A).

268 We also identified a heterozygous splice site variant in the nuclear envelope gene SYNE1 i

269 Analysis of one splice site variant showed an in-frame insertion of 12 b

270 onymous and 1% gain or loss of stop codon or splice site variant] in 16 751 genes with the strongest

271 2_Glyfs( *)51]) in one family and a putative splice-site variant (c.3985+5C>A) in the other.

272 mphoblasts from the patient carrying a SYNE1 splice-site variant displayed changes in nuclear morphol

273 n spectrum includes frameshift, missense and splice site variants and one single-exon deletion.

274 assays were performed for two non-canonical splice site variants and revealed missplicing for the mu

275 ass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to

276 Germline nonsense and canonical splice site variants identified in disease-causing genes

277 cted 28 low-frequency missense, nonsense and splice site variants that were enriched in the pre-eclam

278 matic variants including missense mutations, splice site variants, frameshift indels, and stop gain/l

279 signs of PRA did not identify any exonic or splice site variants, suggesting the causal variant was

280 RNA analysis of splice-site variants can assist in understanding pathoge

281 We found 29 rare MYBPC3 splice-site variants in 56 of 557 (10%) unrelated HCM pr

282 We evaluated the contribution of MYBPC3 splice-site variants in a large cohort of patients with

283 Novel non-synonymous/splice-site variants in extracellular matrix genes were

284 e patients harbored heterozygous nonsense or splice-site variants in the nucleoporin genes NUP37, NUP

285 Rare missense, truncating or splice-site variants shared by the 3 relatives were sele

286 analysis, 4 of 56 (7%) families with MYBPC3 splice-site variants were reclassified from uncertain cl

287 ns were defined as nonsense, frameshift, and splice-site variants, along with missense variants resul

288 s or compound heterozygous) nonsynonymous or splice-site variations in 6 cardiomyopathy-associated ge

289 dition, in mutant RNA substrates, the new 3' splice site was preferentially recognized compared with

290 Cassette exons and alternative 3' splice sites were the most frequently found alternativel

291 ow likely distant mutations around annotated splice sites were to disrupt splicing.

292 nce between their lariat branch point and 3' splice site, which is necessary and sufficient for their

293 positions 120739/121012 and encodes a single splice site, which is shared with the 3'-coterminal K14-

294 The splicing reaction requires definition of splice sites, which are initially recognized in either i

295 f S34F caused a shift in cross-linking at 3' splice sites, which was significantly associated with al

296 king, and restructures the pairing of the 5' splice site with the U6 snRNA ACAGAGA region.

297 Patients with variants in MYBPC3 splice sites with in silico-predicted effects on splicin

298 c variant in a non-canonical, well-conserved splice site within TRAPPC4 (hg19:chr11:g.118890966A>G; T

299 d emerge by the appearance of new functional splice sites within an extant intron.

300 licing have revealed the presence of cryptic splice sites within the halpha-globin gene transcript.