ライフサイエンスコーパス: readthrough

1 D gene family (FXYD1, FXYD6, and FXYD6-FXYD2 readthrough).

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

3 messenger RNAs resulting from RNA polymerase readthrough.

4 ns are likely required to regulate ribosomal readthrough.

5 ults in defective NNS termination and Pol II readthrough.

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

7 ng, particularly for those viruses employing readthrough.

8 stop codon contribute to this high level of readthrough.

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

10 e first genome-wide experimental analysis of readthrough.

11 gulated by transcriptional and translational readthrough.

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

13 iral RNA elements that promote translational readthrough.

14 manner that is reproducible by translational readthrough.

15 ents resulted in differential effects on UGA readthrough.

16 ne structures, including abundant stop-codon readthrough.

17 minally extended polypeptides via stop-codon readthrough.

18 ations caused by splicing or transcriptional readthrough.

19 uced (K108E) or increased (R116D) stop codon readthrough.

20 ntrol translation termination and stop codon readthrough.

21 ing the need for systematic investigation 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 Escin, an herbal agent, consistently induced readthrough activity as demonstrated by enhanced CFTR ex

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

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

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

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

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

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

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

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

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

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

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

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

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

39 rA4G) RSV mutant resulted in transcriptional readthrough and lower G and fusion (F) protein levels th

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

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

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

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

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

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

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

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

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

49 We verify ARTDeco's ability to detect readthrough as well as identify read-in genes from diffe

50 y assessing bulk protein synthesis kinetics, readthrough, assembly, and structure mapping.

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

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

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

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

55 however, does not result in transcriptional readthrough at the majority of piRNA loci.

56 termination and are important regulators of readthrough at the premature termination codon.

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

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

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

60 of YARIS for systematic study of translation readthrough by employing it to interrogate the effects o

61 We also modulated readthrough by silencing expression of eukaryotic releas

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

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

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

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

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

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

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

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

70 proach to identify a further three mammalian readthrough candidates.

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

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

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

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

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

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

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

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

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

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

81 and novel transcripts created as a result of readthrough (downstream of gene or DoG transcripts).

82 We tested both small-molecule readthrough drug and gene-therapy approaches for this "d

83 After readthrough drug treatment, the LCA16 hiPSC cells were h

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

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

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

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

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

89 Readthrough efficiency was not affected by the stop codo

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

91 the effect on MuLV replication of modulating readthrough efficiency.

92 with Sec incorporation factors to determine readthrough efficiency.

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

94 of eEF2K decreases misreading or termination readthrough errors during elongation, whereas knocking d

95 GO1 stop codon, which is sufficient to drive readthrough even in a heterologous context.

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

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

98 Such readthrough events can be therapeutically desirable when

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

100 The readthrough-extended lactate dehydrogenase subunit LDHBx

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

102 eased translational miscoding and stop codon readthrough frequencies.

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

104 Translational readthrough generates proteins with extended C-termini,

105 ies individual genes that fail to terminate (readthrough genes), are aberrantly transcribed due to up

106 which causes very extensive transcriptional readthrough genome-wide.

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

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

109 emature termination codons in human disease, readthrough has emerged as an attractive therapeutic tar

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

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

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

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

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

115 hese mechanisms contributes to translational readthrough in Saccharomyces cerevisiae.

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

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

118 1) activity, the inhibition of which extends readthrough in the absence of XRN2.

119 a complete group of yeast tRNAs that induce readthrough in the stop-codon tetranucleotide manner whe

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

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

122 monstrates the complexity of response to PTC readthrough inducers.

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

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

125 As are the keystones of YARIS (yeast applied readthrough inducing system), a reporter-based assay ena

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

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

128 l rti-tRNA modifications, as well as various readthrough-inducing drugs (RTIDs).

129 eotide manner when overexpressed, designated readthrough-inducing tRNAs (rti-tRNAs).

130 pecific manner by promoting incorporation of readthrough-inducing tRNAs.

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

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

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

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

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

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

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

138 Readthrough is far more pervasive than expected: the vas

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

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

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

142 equence has a let-7a miRNA-binding site, and readthrough is promoted by let-7a miRNA.

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

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

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

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

147 mplexes and release factors perturbs the UGA readthrough level.

148 sed assay enabling simultaneous detection of readthrough levels at all twelve stop-codon tetranucleot

149 Readthrough levels further increased to 12% when tested

150 mediately following the stop codon, modulate readthrough levels, underscoring the need for systematic

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

152 g that targeting of critical stop codons for readthrough may be achievable without general disruption

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

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

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

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

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

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

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

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

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

162 the abundances of individual viral mRNAs and readthrough mRNAs.

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

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

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

166 Translational readthrough, observed primarily in less complex organism

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

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

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

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

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

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

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 reporter assays to demonstrate translational readthrough of AGO1 mRNA.

176 ovided additional evidence for translational readthrough of AGO1.

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

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

179 es of Xist (Xist-2kb) causes transcriptional readthrough of downstream polyadenylation sequences.

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

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

182 adthrough of PTCs, aminoglycosides stimulate readthrough of normal termination codons (NTCs) genome-w

183 Readthrough of NusA-dependent terminators caused misregu

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

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

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

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

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

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

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

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

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

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

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

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

196 nown function to induce eukaryotic ribosomal readthrough of PTCs to produce a full-length protein.

197 We find that in addition to stimulating readthrough of PTCs, aminoglycosides stimulate readthrou

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

199 duced by the SecM stalling sequence and that readthrough of SecM directly correlates with the stabili

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

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

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

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

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

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

206 histone mutants that exhibit transcriptional readthrough of terminators.

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

208 Translational readthrough of the premature stop codon was demonstrated

209 Readthrough of these RNAs into the intended transcriptio

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

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

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

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

214 ed central spine, permitting transcriptional readthrough or translation initiation.

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

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

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

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

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

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

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

222 uppressed (R116D) or exacerbated (K108E) the readthrough phenotypes, and partially corrected or exace

223 o robustly quantifies the global severity of readthrough phenotypes, and reliably identifies individu

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

225 This readthrough process is directed by a cis sequence downst

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

227 miRNA pathway mediated by the translational readthrough product of AGO1.

228 The endogenous readthrough product, Ago1x, could be detected by a speci

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

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

231 oof-of-concept that aminoglycosides or other readthrough-promoting compounds are a therapeutic avenue

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

233 The progranulin readthrough protein displayed similar subcellular locali

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

235 The resulting readthrough proteins retain function and contain amino a

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

237 Combining these two mutations with the readthrough-reducing mutations at the extreme C-terminus

238 FP tagging and mass spectrometry for several readthrough regions.

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

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

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

242 Readthrough required Repeat A and the ~750 nucleotides d

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

244 Stop codon readthrough (SCR) occurs when the ribosome miscodes at a

245 amino acids in a process known as stop codon readthrough (SCR), producing extended protein isoforms w

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

247 tudy, we tested the only clinically approved readthrough small molecule PTC124 and 11 aminoglycosides

248 The aminoglycoside-induced readthrough strategy has been utilized to treat multiple

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

250 nalysis revealed AGO1 and MTCH2 as authentic readthrough targets.

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

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

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

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

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

256 Stop codon readthrough-the decoding of a stop codon by a near-cogna

257 Using either readthrough therapy or gene augmentation, we rescued Kir

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

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

260 Readthrough thus provides general mechanisms both to reg

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

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

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

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

265 creases nucleosome occupancy in vivo reduced readthrough transcription and suppressed the effect of a

266 We developed Automatic Readthrough Transcription Detection (ARTDeco), a tool to

267 l to detect and analyze multiple features of readthrough transcription from RNA-seq and other next-ge

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

269 ARTDeco aids researchers investigating readthrough transcription in a variety of systems and co

270 This indicates that taking readthrough transcription into account is important for

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

272 We used ARTDeco to characterize readthrough transcription observed during influenza A vi

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

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

275 uption of transcription termination leads to readthrough transcription past the 3' end of genes, whic

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

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

278 This is because readthrough transcripts now extend into downstream genes

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

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

281 reporter activity and levels of such spliced readthrough transcripts.

282 ant RNA confirmed the presence of terminator readthrough transcripts.

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

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

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

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

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

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

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

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

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

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

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

294 5-fold stimulation of readthrough (up to 60% readthrough) was well tolerated by the virus.

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

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

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

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,