ライフサイエンスコーパス: readthrough

1 , substrate reduction therapy, or stop codon readthrough).

2 RNA oligo(U) 3'-end cleavage, and terminator readthrough.

3 e first genome-wide experimental analysis of readthrough.

4 s frameshifts, ribosome hops, and stop codon readthrough.

5 iral RNA elements that promote translational readthrough.

6 manner that is reproducible by translational readthrough.

7 ents resulted in differential effects on UGA readthrough.

8 ne structures, including abundant stop-codon readthrough.

9 minally extended polypeptides via stop-codon readthrough.

10 correlation with known effects on stop codon readthrough.

11 don positions after the ORF, acting to limit readthrough.

12 E1b promoter suppressed the requirement for readthrough.

13 ed for an appropriate level of translational readthrough.

14 version of the sequence abolished terminator readthrough.

15 sequences the mechanism used is a bona fide readthrough.

16 s showed that Qa RNA abolished transcription readthrough.

17 ns are likely required to regulate ribosomal readthrough.

18 ults in defective NNS termination and Pol II readthrough.

19 hnRNP) A2/B1 binds this element and promotes readthrough.

20 ng, particularly for those viruses employing readthrough.

21 stop codon contribute to this high level of readthrough.

22 covering 149 possible examples of stop codon readthrough, 125 new candidate ORFs of polycistronic mRN

23 inistration of gentamicin with PAA increased readthrough 20-40% relative to cells treated with the sa

24 Transcript readthrough accounts for the absence of changes in DNA m

25 ns and E1a enhancer mutations suggested that readthrough activation and E1a enhancer activation of th

26 These results suggest that readthrough activation is a "local" effect of a direct i

27 facilitate further study of the mechanism of readthrough activation, the activities of GGT and a comp

28 Escin, an herbal agent, consistently induced readthrough activity as demonstrated by enhanced CFTR ex

29 onents of pharmaceutical gentamicin lack PTC readthrough activity but the minor component gentamicin

30 st, we demonstrated that gentamicin enhanced readthrough activity in cells transfected with SERPINB7

31 The two compounds also demonstrated readthrough activity in mdx mouse myotube cells carrying

32 iable and major gentamicins suppress the PTC readthrough activity of B1.

33 doses of this drug produce weak and variable readthrough activity that is insufficient for use as the

34 des a consistent and effective source of PTC readthrough activity to study the potential of nonsense

35 r-mass nonaminoglycosides with potential PTC-readthrough activity.

36 in vivo (25%-60%); (2) increased stop codon readthrough activity; (3) increased sensitivity to ribos

37 cally approved drugs identified as potential readthrough agents, in combination with ivacaftor, may i

38 , including alternative splicing, stop codon readthrough, alternative translation initiation, and C-t

39 a distinct class with weaker phenotype, less readthrough and 3'-oligo(U) lengthening.

40 ommon transcripts, but also by transcription readthrough and capture of nearby exons.

41 recoding of reporters containing retroviral readthrough and frameshift sequences, as well as the Sin

42 utants have strong phenotypes with up to 40% readthrough and map to a C-terminal tract previously loc

43 but that on a molar basis, the levels of the readthrough and pnp transcripts were considerably lower

44 Ratios of encapsidated readthrough and polyadenylated transcripts for vectors w

45 term gentamicin dosing to achieve stop codon readthrough and produce full-length dystrophin.

46 There was a strict correlation between readthrough and substantial downstream gene expression,

47 sed antibiotic in humans that can induce PTC readthrough and suppress nonsense mutations at high conc

48 lly significant suppression (< 2% stop codon readthrough); and two appear refractory to aminoglycosid

49 Four displayed efficient stop codon readthrough, and these have UGA immediately followed by

50 tor, displayed extremely efficient levels of readthrough ( approximately 31%) in HEK-293T cells.

51 s C-terminus, the potential of translational readthrough as a therapeutic mechanism for SMA is unclea

52 st in vivo evidence supporting translational readthrough as a therapeutic strategy for the treatment

53 poration is able to repress G418-induced UGA readthrough as well as eRF1-induced stimulation of termi

54 Using a sensitive and versatile readthrough assay in conjunction with RNA interference t

55 hort RNAs causes a decrease in translational readthrough at a stop codon, and ribosomes on repressed

56 B1 induced readthrough at all three nonsense codons in cultured can

57 is, we found that depletion of eRF1 enhances readthrough at all three stop codons in 293 cells and He

58 n readthrough in 293 cells but does increase readthrough at all three stop codons in HeLa cells.

59 context in determining the efficiency of UGA readthrough at each of the 10 rat Sel P Sec codons, we i

60 nt with this finding, loci exhibiting Pol II readthrough at GRF binding sites are depleted for upstre

61 In addition, readthrough at UGA was observed when the viral SECIS ele

62 in the absence of TFIIS were reactivated to readthrough blocks to elongation.

63 observe massive induction of transcriptional readthrough, both in levels and length, under all stress

64 nd isolated many C37 mutants with terminator readthrough but no comparable C53 mutants.

65 We also modulated readthrough by silencing expression of eukaryotic releas

66 re demonstrated that the stem-loop increases readthrough by up to 10-fold.

67 than being a translation 'error', stop-codon readthrough can have important effects on other cellular

68 ression of stop codons (termed translational readthrough) can be caused by a decreased accuracy of tr

69 e genomic analysis revealed that in the four readthrough candidates containing UGA-CUAG, this motif i

70 We find that the set of readthrough candidates differs from other genes in lengt

71 sect species and one crustacean, and several readthrough candidates in nematode and human, suggesting

72 n for assessing the large number of cellular readthrough candidates that are currently being revealed

73 We report an expanded set of 283 readthrough candidates, including 16 double-readthrough

74 proach to identify a further three mammalian readthrough candidates.

75 readthrough candidates, including 16 double-readthrough candidates; these were manually curated to r

76 in Drosophila, only a very limited number of readthrough cases in chromosomal genes had been reported

77 tures feature in a much larger proportion of readthrough cases than previously anticipated, and provi

78 ent assay (ELISA), for identifying novel PTC-readthrough compounds using ataxia-telangiectasia (A-T)

79 work reported that the signal for efficient readthrough comprises a single cytidine residue 3'-adjac

80 escribed can be employed to define potential readthrough contexts for any genome.

81 tly prolonged the time interval during which readthrough could be detected, as shown by short circuit

82 tors in the GUS transgene 3' reduced mRNA 3' readthrough, decreased GUS-specific small interfering RN

83 ranslation, but they can be read as 'sense' (readthrough) depending on their context, comprising the

84 of PTC in a transfected vector revealed that readthrough depends on the PTC sequence and its location

85 The efficiency of aminoglycoside-mediated readthrough depends on the type and copy number of PTC,

86 use of genetic or chemical means to increase readthrough does not promote novel or alternative mispai

87 of the mutant locus is a failure to produce readthrough dsRNA methylation triggers.

88 el or alternative mispairing events; rather, readthrough effectors cause quantitative enhancement of

89 While we were able to confirm the readthrough efficacy of the 2 drugs in Human Embryonic K

90 is of this region, and we quantified in vivo readthrough efficiency for each alanine mutant.

91 is of the effect of increasing or decreasing readthrough efficiency on virus replication using the ga

92 assays, it was found that reducing the MuLV readthrough efficiency only 4-fold led to a marked defec

93 Readthrough efficiency was not affected by the stop codo

94 differences, spanning an 8-fold range of UGA readthrough efficiency, were observed, but these differe

95 the effect on MuLV replication of modulating readthrough efficiency.

96 with Sec incorporation factors to determine readthrough efficiency.

97 The immunogenic epitope resulting from readthrough emphasizes the importance of monitoring T-ce

98 Although the major readthrough event at the UGA codon was insertion of tryp

99 er of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlappin

100 ervasive than expected: the vast majority of readthrough events evolved within D. melanogaster and we

101 Increased readthrough expression of rocG was shown to be partially

102 The readthrough-extended lactate dehydrogenase subunit LDHBx

103 gh RTP by using this model, and analyzed all readthrough extensions in silico with a new predictor fo

104 ightly inhibited by substantial increases in readthrough frequency, but as with other viruses that us

105 Translational readthrough gives rise to low abundance proteins with C-

106 cells, and individual cells with higher UGA readthrough grow faster from stationary phase.

107 and increase both the level and duration of readthrough has important implications for this promisin

108 ions of translational components lead to UGA readthrough heterogeneity among single cells, which enha

109 depletion of eRF3 has little or no effect on readthrough in 293 cells but does increase readthrough a

110 RNA structures are likely to be relevant to readthrough in certain plant virus genera, notably Furov

111 elanogaster, but the importance of regulated readthrough in eukaryotes remains largely unexplored.

112 c workflow that enabled the detection of UAG readthrough in native proteins in E. coli strains in whi

113 hese mechanisms contributes to translational readthrough in Saccharomyces cerevisiae.

114 ond Drosophila and find evidence of abundant readthrough in several other insect species and one crus

115 uence, there was little effect on terminator readthrough in the absence of NusB.

116 upper stem variant has significantly higher readthrough in the context of a paired, rather than unpa

117 equally as effective in promoting stop codon readthrough in vivo, readthrough which in both cases res

118 Alternatively, readthrough, in which the stop codon is erroneously deco

119 th significant, yet not complete, overlap of readthrough-induced loci between different conditions.

120 nor component gentamicin B1 (B1) is a potent readthrough inducer.

121 monstrates the complexity of response to PTC readthrough inducers.

122 subsequently treated with two translational readthrough inducing drugs (G418 & PTC124) to investigat

123 ense suppression therapy using translational readthrough inducing drugs may provide functional rescue

124 as distinct for specific nonsense codons and readthrough-inducing agents.

125 s, we investigated the responsiveness to the readthrough-inducing drug geneticin of 11 rationally sel

126 us parent transposon by deletion followed by readthrough into an adjacent gene and its promoter, thus

127 m mRNAs lacking stop codons or translational readthrough into the poly(A) tail.

128 Thus selection against stop codon readthrough is a dominant force acting on 3', but not on

129 Programmed stop codon readthrough is a post-transcription regulatory mechanism

130 Importantly, the eIF3 role in programmed readthrough is conserved between yeast and humans.

131 The relative frequency of termination versus readthrough is determined by parameters such as the stop

132 We clearly demonstrate that efficient readthrough is enabled by near-cognate tRNAs with a mism

133 nse codons and that, irrespective of whether readthrough is endogenous or induced, the same sets of a

134 Stop codon readthrough is essential to diverse viruses, and phyloge

135 Readthrough is far more pervasive than expected: the vas

136 porter system, we discovered that stop codon readthrough is heterogeneous among single cells, and ind

137 suggest that stress-induced transcriptional readthrough is not a random failure process, but is rath

138 While translational stop codon readthrough is often used by viral genomes, it has been

139 subcellular localization signals, and their readthrough is regulated, arguing for their importance.

140 d by a UAG stop codon, and termination codon readthrough is required for expression of the viral Gag-

141 ctionally important translational stop codon readthrough is significantly more prevalent in Metazoa t

142 Stop codon readthrough is used extensively by viruses to expand the

143 mplexes and release factors perturbs the UGA readthrough level.

144 Readthrough levels do not substantially vary between dif

145 Readthrough levels further increased to 12% when tested

146 We report the translational readthrough levels induced by the aminoglycosides gentam

147 this insert shifts F gene transcription from readthrough M-F mRNA to monocistronic F mRNA.

148 cture and parameters governing effective PTC readthrough may provide a unique prophylactic therapy fo

149 TCs, impaired secretion/function produced by readthrough-mediated amino acid substitutions prevented

150 fold increased activity of the most probable readthrough-mediated missense variant (rFIX-R384W).

151 servation signature, hinting that stop codon readthrough might be common in Drosophila.

152 he M-GE mutants exhibited a reduction in M-F readthrough mRNA and an increase in monocistronic F mRNA

153 ription terminator produced unpolyadenylated readthrough mRNA and consistent RDR6-dependent RNA silen

154 nction, thus promoting the production of M-F readthrough mRNA at the expense of monocistronic F mRNA.

155 was associated with increased synthesis of a readthrough mRNA of the M gene and the downstream F gene

156 We show that readthrough mRNA synthesis occurs in EBOV-infected cells

157 TE of the NS1 GE increased the production of readthrough mRNAs concomitant with a decrease of monocis

158 displayed increased levels of polycistronic readthrough mRNAs resulting from failure of the polymera

159 ased production of the related polycistronic readthrough mRNAs, which normally arise due to the failu

160 A selection for cis-acting terminator readthrough mutations identified conserved features of t

161 nts similar to those derived from endogenous readthrough, namely Gln, Lys, or Tyr at UAA or UAG PTCs

162 ledge of the amino acids incorporated during readthrough not only elucidates the decoding process but

163 Translational readthrough, observed primarily in less complex organism

164 We further demonstrate that readthrough occurs in yeast and humans.

165 protein P1234 is produced when translational readthrough occurs or when the opal termination codon ha

166 ion systems in nonpermissive cells, enhanced readthrough of (pA)p and the polyadenylation of B19 viru

167 tigated an agent that promotes translational readthrough of a BMPR2 nonsense reporter construct witho

168 ify mutations that decreased transcriptional readthrough of a defective GAL10 poly(A) terminator.

169 rged tRNA to the nascent transcript promotes readthrough of a leader region transcription termination

170 These activities require the readthrough of a leaky viral polyadenylation signal loca

171 Readthrough of a PTC allows ribosomal A-site insertion o

172 on of RT in trans enhanced the translational readthrough of a reporter construct containing the Gag-P

173 gene in this family exhibits an increase in readthrough of a termination signal located upstream of

174 usion with other non-structural proteins via readthrough of a UGA stop codon.

175 ction for trans-acting mutations that induce readthrough of both a snoRNA and an mRNA terminator yiel

176 lement within the eps operon is required for readthrough of distally located termination signals.

177 stop codons identified potential stop codon readthrough of four mammalian genes.

178 We also find that the EAR element promotes readthrough of heterologous termination sites.

179 Readthrough of NusA-dependent terminators caused misregu

180 response to the UAG codon without increasing readthrough of other stop codons.

181 and the minor P3/P5 protein, a translational readthrough of P3.

182 ment must be nonconsensus to allow efficient readthrough of P6-generated pre-mRNAs into the capsid-co

183 solution of stalled ribosomes and subsequent readthrough of poly(A)-containing stall sequences.

184 al entity that selectively induces ribosomal readthrough of premature but not normal termination codo

185 ration of gentamicin with PAA influenced the readthrough of premature stop codons in cultured cells a

186 s have been reported to induce translational readthrough of premature stop codons resulting in the pr

187 onsense mutations for which compound-induced readthrough of premature termination codons (PTCs) might

188 n orally bioavailable compound that promotes readthrough of premature translation termination codons,

189 thway stabilizes nonsense mRNAs and promotes readthrough of premature translation termination codons.

190 se RNAs, as well as the resulting effects on readthrough of prgQ transcription, has been limited.

191 oposed for restoring full-length proteins by readthrough of PTC.

192 which enhances the pace and also facilitates readthrough of roadblocks in vivo.

193 maternal-effect nonsense suppression due to readthrough of stop codons and are zygotically lethal du

194 vels of frameshifting, missense decoding and readthrough of stop codons during the elongation phase o

195 he TPA1 gene (tpa1Delta) exhibited increased readthrough of stop codons, and coimmunoprecipitation as

196 ciated with extremely slow growth, increased readthrough of stop codons, and defects in 50S ribosomal

197 ed by reduced serum CK favoring drug-induced readthrough of stop codons.

198 gene expression directly and indirectly via readthrough of suboptimal terminators.

199 h decrease translational fidelity to promote readthrough of termination codons, were shown to increas

200 showed that it regulated the transcriptional readthrough of termination sites located within two diff

201 and the production of a truncated protein or readthrough of the premature stop codon and production o

202 Translational readthrough of the premature stop codon was demonstrated

203 Readthrough of these RNAs into the intended transcriptio

204 We have recently reported translational readthrough of VEGFA mRNA whereby translating ribosomes

205 y eIF3, which critically promotes programmed readthrough on all three stop codons.

206 ing is used by RNA viruses for translational readthrough or frameshifting past termination codons for

207 ducts arising as a consequence of endogenous readthrough or the compromised termination fidelity attr

208 Two competing events, termination and readthrough (or nonsense suppression), can occur when a

209 nsertion of an amino acid at the stop codon (readthrough) or by alteration of the mRNA reading frame

210 Drug-induced readthrough over premature stop codons (PTCs) is a poten

211 nor, and 281 nt upstream of (pA)p, primarily readthrough (pA)p, are polyadenylated at a more distal s

212 Among the predicted readthrough-permissive TGA variants, only 2 (p.W240X and

213 However, how widespread the readthrough phenomenon is, and what its causes and conse

214 of these distinct processes contributes to a readthrough phenotype has limited our ability to evaluat

215 on run-on analysis confirmed a transcription readthrough phenotype in the absence of Srb5/Med18.

216 longation factors Spt4 and Spt6 suppress the readthrough phenotype, presumably by decreasing the amou

217 protein was found to be responsible for the readthrough phenotype.

218 These studies provide insights into both the readthrough process and MuLV replication and have implic

219 s, together with the observation of a likely readthrough product from a lin-1(e1275)::gfp fusion tran

220 ication and sequence analysis of full-length readthrough products arising as a consequence of endogen

221 those applicable to alternative splices and readthrough products generated by the yeast prion [PSI+]

222 translational readthrough, we estimated the readthrough propensity (RTP) of all stop codon contexts

223 ay allow predictions of the functionality of readthrough protein products.

224 The resulting readthrough proteins retain function and contain amino a

225 ial cells undergoes programmed translational readthrough (PTR) generating VEGF-Ax, an isoform contain

226 rs to modulate the balance of termination to readthrough reactions in a cell-type-specific manner.

227 FP tagging and mass spectrometry for several readthrough regions.

228 conserved stem-loops, providing clues about readthrough regulation and potential mechanisms.

229 Using a dual luciferase readthrough reporter system in cultured cells, we found

230 incorporation reporter in conjunction with a readthrough reporter system to show that alterations at

231 ibe the combined use of misincorporation and readthrough reporter systems to determine which of these

232 t only slight defects in global translation, readthrough, ribosome biogenesis, and programmed ribosom

233 We examined the structure of the trp leader readthrough RNA in the absence of TRAP.

234 ching between viral RNAs and polyadenylation readthrough sequences is responsible for the generation

235 We began by manipulating the readthrough signal in the context of an infectious viral

236 Translational readthrough--suppression of termination at a stop codon-

237 vector "body" sequences) and polyadenylation readthrough "tail" sequences were made highly homologous

238 nalysis revealed AGO1 and MTCH2 as authentic readthrough targets.

239 izosaccharomyces pombe that cause pol III to readthrough terminators in vivo.

240 t 5 retained a significantly higher level of readthrough than context 1.

241 d significantly better (up to 10% stop codon readthrough) than the others; five show lower but statis

242 lso uncover multiple instances of stop-codon readthrough that are conserved between species.

243 protein-regulated, programmed translational readthrough that generates a protein with a known functi

244 o be intrinsically weak, with a low level of readthrough that is enhanced when translation terminatio

245 pletion of dPcf11 with RNAi causes Pol II to readthrough the normal region of termination.

246 hat can maximize the translational value of "readthrough therapy" while mitigating drug-induced side

247 ermine whether topical nonsense-suppression (readthrough) therapy using gentamicin is applicable to N

248 Readthrough thus provides general mechanisms both to reg

249 d that this interaction promotes translation readthrough to make Gag-Pol.

250 es use ribosomal frameshifting or stop codon readthrough to regulate expression of their replicase en

251 owever, our analysis suggests that while the readthrough transcript observed in S. antibioticus may b

252 associated with an increased synthesis of a readthrough transcript of the M gene and the downstream

253 e secondary structure of the S. antibioticus readthrough transcript predicts a stem-loop structure an

254 frequencies were found to correlate with the readthrough transcript prevalence.

255 n Escherichia coli, where observation of the readthrough transcript requires mutants lacking RNase II

256 t least two promoters, the first producing a readthrough transcript that includes both pnp and the ge

257 The pattern of regulation of the readthrough transcript was consistent with transcription

258 and stationary phases, and the levels of the readthrough transcript, initiated upstream of rpsO in th

259 ificantly, however, as judged by evidence of readthrough transcription across the kilB promoter regio

260 Finally, we examine genomic features of readthrough transcription and observe a unique chromatin

261 that disruption of the NRS sequence promotes readthrough transcription and splicing to the downstream

262 es with exosome mutants, including increased readthrough transcription from several mRNA and sn/snoRN

263 mature polyadenylation signal and suppresses readthrough transcription into palindromic PAI sequences

264 al of DoG-producing regions, suggesting that readthrough transcription is associated with the mainten

265 n ecfR which likely reduces the frequency of readthrough transcription of bfrH from the Fe-dependent

266 Blockage of readthrough transcription of E1a had no apparent effect

267 ed Xrn2 chromatin localization and increased readthrough transcription of endogenous genes.

268 the adenovirus 5 E1b gene promoter requires readthrough transcription originating from the adjacent

269 reign DNA, thereby controlling for potential readthrough transcription past the cpIAP insert; and (ii

270 CcpA-dependent repression of rocG readthrough transcription proved to contribute to the sl

271 s, and antisense transcription and pervasive readthrough transcription throughout the genome.

272 cG was still expressed at a low level due to readthrough transcription.

273 complex that was assembled in the absence of readthrough transcription.

274 ermination mechanisms trigger degradation of readthrough transcripts by the exosome.

275 equires mutants lacking RNase III, we detect readthrough transcripts in wild-type S. antibioticus myc

276 This is because readthrough transcripts now extend into downstream genes

277 nic reporter assays by causing these cryptic readthrough transcripts to splice in patterns that allow

278 induction of a subset of heat shock-induced readthrough transcripts.

279 reporter activity and levels of such spliced readthrough transcripts.

280 ant RNA confirmed the presence of terminator readthrough transcripts.

281 genomic rearrangements, as well as 12 novel readthrough transcripts.

282 genuine HIV RNA but rather chimeric host-HIV readthrough transcripts.

283 The [PSI(+)] prion causes widespread readthrough translation and is rare in natural populatio

284 s of the yeast prion [PSI+] cause genomewide readthrough translation that sometimes increases evolvab

285 er isoform, VEGF-Ax, arising from programmed readthrough translation.

286 To identify novel contexts directing readthrough, under-represented 5' and 3' stop codon cont

287 The sequence UGA-CUA alone can support 1.5% readthrough, underlying its importance.

288 to an approximately 8.5-fold stimulation of readthrough (up to 60% readthrough) was well tolerated b

289 was reported to result from transcriptional readthrough upon osmotic stress in human cells.

290 ent a genome-wide mapping of transcriptional readthrough, using nuclear RNA-Seq, comparing heat shock

291 No such terminator readthrough was observed in the mutant at the permissive

292 generate a series of MuLV variants in which readthrough was stimulated or reduced.

293 5-fold stimulation of readthrough (up to 60% readthrough) was well tolerated by the virus.

294 To identify functional translational readthrough, we estimated the readthrough propensity (RT

295 To assess the efficiency of readthrough, we selected homozygous and compound heteroz

296 These high levels of readthrough were achieved using a two-plasmid system, wi

297 in promoting stop codon readthrough in vivo, readthrough which in both cases responded identically to

298 rotein synthesis levels exhibited higher UGA readthrough, which was confirmed with ribosome-targeting

299 frameshifting, antiviral therapies targeting readthrough with inhibitory agents are likely to be the

300 n vitro cell-based assays showed significant readthrough with two drugs, gentamicin and paromomycin,