ライフサイエンスコーパス: NMD

1 NMD also limits the efficacy of read-through compound (R

2 NMD components, including smg-2/UPF1, are required to ac

3 NMD in the nervous system of the animals is particularly

4 NMD is essential for viability in most organisms, but th

5 NMD is regulated in a tissue-specific and developmentall

6 NMD modulates the clinical outcome of a variety of human

7 NMD suppression by persistent DNA damage required the ac

8 NMD surveillance, however, does not entirely explain the

9 NMD-elicit mutations in tumour suppressor genes (TSGs) a

10 ly conserved cassette exons, including 1,014 NMD exons that may function directly to control gene exp

11 fect UPF1 phosphorylation and hence abrogate NMD.

12 Although NMD-induced loss-of-function has been shown to contribut

13 Activating transcription factor 3 (ATF3), an NMD target and a key stress-inducible transcription fact

14 on of certain stress response networks in an NMD mutant could be linked to disequilibrium between fun

15 on of certain stress response networks in an NMD mutant could be linked to disequilibrium between fun

16 RNA compared to the wild-type minigene in an NMD-dependent manner.

17 lation of yars-2/tyrosyl-tRNA synthetase, an NMD target transcript, by daf-2 mutations contributes to

18 ATP hydrolysis-dependent mechanism until an NMD target is identified.

19 eover, requires ATP-binding, RNA-binding and NMD cofactors UPF2 and UPF3.

20 egulate p53beta in a synergistic manner, and NMD plays a critical role in the determination of the p5

21 on factor, was stabilized in a p38alpha- and NMD-dependent manner following persistent DNA damage.

22 ance of concerted repression by splicing and NMD.

23 les in premature translation termination and NMD.

24 ctional relationship between translation and NMD.

25 al accumulation of RNAs normally degraded as NMD substrates.

26 nding of RNA surveillance mechanisms such as NMD and crucial for the development of therapeutic strat

27 nition of PTC-containing hERG transcripts as NMD substrates have not been established.

28 diagnosis of heterogeneous disorders such as NMDs, targeted panel testing has the highest clinical yi

29 pling of AS with nonsense-mediated decay (AS-NMD).

30 that can specifically and effectively assay NMD in live human cells.

31 dent mRNA translation, rapamycin can augment NMD of certain transcripts.

32 ohorts (United Dystrophinopathy Project, Bio-NMD, and Padova, total n = 660), establishing this locus

33 minate accumulation of NMD complexes on both NMD target and non-target mRNAs.

34 DUX4 mRNA is itself degraded by NMD, such that inhibition of NMD by DUX4 protein stabili

35 of the pervasive transcripts are degraded by NMD, which provides a fail-safe mechanism to remove spur

36 bserved for AS events that are detectable by NMD as well as for those that are not, which invalidates

37 apamycin modulates global RNA homeostasis by NMD.

38 Regulation of HR by NMD extends to multiple targets beyond RAD55, including

39 anscript and protein levels are regulated by NMD.

40 to the mechanisms by which mRNAs targeted by NMD are degraded.

41 elimination of PTC-containing transcripts by NMD required that the mutation be positioned >54-60 nt u

42 te UPF1 binding is not a marker for cellular NMD substrates and how this binding is transformed to in

43 UPF1 is a discriminating marker of cellular NMD targets, unlike for premature termination codon (PTC

44 p-UPF1 provides the first reliable cellular NMD target marker.

45 A central NMD factor is the ATP-dependent RNA helicase upframeshif

46 clinically used chemotherapeutic compounds, NMD activity declines partly as a result of the proteoly

47 Here we show that a single, conserved NMD target, the mRNA coding for the stress response fact

48 that ablation of Upf2, which encodes a core NMD factor, in murine embryonic Sertoli cells (SCs) lead

49 unt for lethality in Drosophila lacking core NMD genes.

50 Phosphorylation of the core NMD component UPF1 is critical for NMD and is regulated

51 evidence for a major function of AS-coupled NMD in shaping the Arabidopsis transcriptome, having fun

52 e the long-term surface recycling of crustal NMD anomalies, and show that the record of this geochemi

53 cted from the National Mammography Database (NMD).

54 Nonsense-mediated decay (NMD) degrades mRNAs containing a premature termination c

55 Nonsense-mediated decay (NMD) eliminates transcripts with premature termination c

56 Nonsense-mediated decay (NMD) is a messenger RNA quality-control pathway triggere

57 Nonsense-mediated decay (NMD) is a posttranscriptional surveillance mechanism in

58 Nonsense-mediated decay (NMD) is an important process that is best known for degr

59 al component of the nonsense-mediated decay (NMD) machinery, is associated with profound NMD inhibiti

60 Nonsense-mediated decay (NMD) provides quality control of mRNA, targeting faulty

61 licase required for nonsense-mediated decay (NMD) regulating mRNA stability in the cytoplasm.

62 es predominating on nonsense-mediated decay (NMD) targets, upstream open reading frames (uORFs), cano

63 TCs), which trigger nonsense-mediated decay (NMD), a cytoplasmic RNA degradation pathway.

64 e last exon, escape nonsense-mediated decay (NMD), and most likely generate a C-terminally truncated

65 not substrates for nonsense-mediated decay (NMD), even though they were detected in polysomes.

66 e central factor in nonsense-mediated decay (NMD), to increasingly attract downstream machinery with

67 ty control process, nonsense-mediated decay (NMD), were found to genetically interact with rad55 phos

68 prime candidate for nonsense-mediated decay (NMD).

69 are not subject to nonsense-mediated decay (NMD).

70 scrimination during nonsense-mediated decay (NMD).

71 nd cannot result in nonsense-mediated decay (NMD).

72 arget the mRNAs for Nonsense-Mediated-Decay (NMD).

73 ere substrates for nonsense-medicated decay (NMD), and could potentially have been stabilized by caff

74 s required for nonsense-mediated mRNA decay (NMD) and promotes translation.

75 Nonsense-mediated mRNA decay (NMD) controls the quality of eukaryotic gene expression

76 pletion of the nonsense-mediated mRNA decay (NMD) factor SMG7 or UPF1 significantly induced p53beta b

77 by hnRNPC and nonsense-mediated mRNA decay (NMD) in the quality control and evolution of new Alu-exo

78 Nonsense-mediated mRNA decay (NMD) is a cellular quality-control mechanism that is tho

79 Nonsense-mediated mRNA decay (NMD) is a cellular surveillance pathway that recognizes

80 Nonsense-mediated mRNA decay (NMD) is a eukaryotic mRNA quality control and regulatory

81 Mammalian nonsense-mediated mRNA decay (NMD) is a eukaryotic surveillance mechanism that degrade

82 Nonsense-mediated mRNA decay (NMD) is a eukaryotic surveillance mechanism that monitor

83 Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and selec

84 Nonsense-mediated mRNA decay (NMD) is a translation-dependent RNA quality-control path

85 Nonsense-mediated mRNA decay (NMD) is an essential eukaryotic process regulating trans

86 ) mutations by nonsense-mediated mRNA decay (NMD) is an important mechanism of long QT syndrome type

87 Nonsense-mediated mRNA decay (NMD) limits the production of aberrant mRNAs containing

88 ase H prevents nonsense-mediated mRNA decay (NMD) of mRNAs.

89 d in mediating nonsense-mediated mRNA decay (NMD) of transcripts containing premature stop codons and

90 We inhibit the nonsense-mediated mRNA decay (NMD) pathway and show that the PTC-containing mRNAs are

91 The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs containing long 3'UTRs to pe

92 The nonsense-mediated mRNA decay (NMD) pathway functions to degrade both abnormal and wild

93 The Nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premat

94 The nonsense-mediated mRNA decay (NMD) pathway selectively eliminates aberrant transcripts

95 Nonsense-mediated mRNA decay (NMD) represents a eukaryotic quality control pathway tha

96 Nonsense-mediated mRNA decay (NMD) represents a highly conserved RNA surveillance mech

97 regulators of nonsense-mediated mRNA decay (NMD), a cytoplasmic surveillance pathway that accelerate

98 ses triggering nonsense-mediated mRNA decay (NMD), a highly conserved RNA degradation pathway.

99 nisms, such as nonsense-mediated mRNA decay (NMD), which degrades both abnormal as well as some norma

100 nscriptomes of nonsense-mediated mRNA decay (NMD)-impaired and heat-stressed plants shared a set of r

101 graded through nonsense-mediated mRNA decay (NMD).

102 tive event in non-sense-mediated mRNA decay (NMD).

103 degradation by nonsense-mediated mRNA decay (NMD).

104 on is known as nonsense-mediated mRNA decay (NMD).

105 onsense-mediated messenger RNA (mRNA) decay (NMD).

106 Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA degradation

107 ntly shown that nonsense-mediated RNA decay (NMD) is inhibited by cellular stresses generated by the

108 omponent of the nonsense-mediated RNA decay (NMD) pathway, in 13 of 15 pulmonary IMT samples.

109 ritical for the nonsense-mediated RNA decay (NMD) pathway, while its autosomal counterpart--UPF3A--en

110 omponent of the nonsense-mediated RNA decay (NMD) pathway.

111 damage inhibits nonsense-mediated RNA decay (NMD), an RNA surveillance and gene-regulatory pathway, i

112 their mRNAs by nonsense-mediated RNA decay (NMD).

113 Non-mass-dependent (NMD) sulphur isotope anomalies in the rock record are th

114 7% PKD2, and 7.6% with no mutation detected (NMD).

115 tion (FMD), nitroglycerin-mediated dilation (NMD), carotid-femoral pulse wave velocity, carotid-radia

116 e and after nitroglycerin-mediated dilation (NMD).

117 ified UPF3B-regulated RNAs, including direct NMD target transcripts encoding proteins with known func

118 Neuromuscular diseases (NMDs) are a group of >200 highly genetically as well as

119 For many neuromuscular diseases (NMDs), cardiac disease represents a major cause of morbi

120 a model in which UPF1 mutations downregulate NMD, leading to NIK-dependent NF-kappaB induction, which

121 berrant p53beta expression and dysfunctional NMD are both implicated in cancers, our studies may prov

122 73 K mutations that are predicted to elicit NMD (NMD-elicit).

123 MG6 cleavage sites in hundreds of endogenous NMD targets in human cells have been mapped at high reso

124 Enhanced NMD activity also correlates with an enrichment of the n

125 We find that daf-2 mutants display enhanced NMD activity and reduced levels of potentially aberrant

126 the translation initiation AUG codon escape NMD.

127 However, some Alu-exons escape NMD, especially when an adjacent intron is retained, hig

128 ting the hypothesis that mutant mRNA escapes NMD.

129 Phosphorylation of the essential NMD effector UPF1 by the phosphoinositide-3-kinase-like

130 degradation of Gadd45 mRNA is the essential NMD function and, surprisingly, that the surveillance of

131 ng to genetic buffering within the essential NMD pathway.

132 However, some PTC-containing mRNAs evade NMD, and might generate mutant proteins responsible for

133 r of NMD and has implications for exploiting NMD in the treatment of disease.

134 the core NMD component UPF1 is critical for NMD and is regulated in mammals by the SURF complex (UPF

135 region in this domain that is essential for NMD and independent of Upf2's binding sites for Upf1 and

136 icase whose ATPase activity is essential for NMD, but for which the precise function and site of acti

137 orylation becomes increasingly important for NMD when downstream factors are depleted.

138 We propose a unified model for NMD in which the Upf factors provide several functions d

139 ing that a downstream intron is required for NMD.

140 Recent findings have revealed a role for NMD in targeting viral RNA molecules, thereby restrictin

141 red systematic forward genetic screening for NMD factors in human cells.

142 s CRISPR-based forward genetic screening for NMD pathway defects in human cells.

143 he development of therapeutic strategies for NMD-related diseases.

144 30%) of PTC-containing mRNAs expressed from NMD-competent PTC-containing constructs were as stable a

145 ct boundary of AUG-proximity protection from NMD.

146 ion of trace amounts of mutant proteins from NMD-competent PTC-containing constructs was not affected

147 fic retroviral and cellular transcripts from NMD.

148 role of RNA helicases in the transition from NMD complexes that recognize a PTC to those that promote

149 s UPF1 phosphorylation leading to functional NMD.

150 e clinical diagnostic yields of single gene (NMD-associated) tests with the various NMD NGS panel tes

151 n generates, for 47% of the expressed genes, NMD-sensitive transcript isoforms carrying uORFs or star

152 ge, sex, race, and dialysis status), greater NMD associated with greater 6-week AVF blood flow rate a

153 How NMD targets are identified is incompletely understood.

154 To explore how NMD shapes the embryonic transcriptome, we integrated ge

155 decades of research, it is still unclear how NMD discriminates between PTCs and normal stop codons.

156 conditionally lacking UPF3A exhibit "hyper" NMD and display defects in embryogenesis and gametogenes

157 We show that in both normal and in NMD-deficient cells, AS rates strongly decrease with inc

158 tive mRNA splicing and pronounced changes in NMD-sensitive isoforms.

159 a transcript, which was further confirmed in NMD reporter gene assays.

160 AVF diameter (per absolute 10% difference in NMD: change in blood flow rate =14.0%; 95% confidence in

161 6G>T mutation in family 132 should result in NMD in transcripts from either TSS.

162 se-like kinase (PIKK) SMG-1 is a key step in NMD and occurs when SMG-1, its two regulatory factors SM

163 spho-UPF1, the single most important step in NMD.

164 The management of cardiac disease in NMDs is made challenging by the broad clinical heterogen

165 in this conserved region not only inactivate NMD but also disrupt Upf2 binding to specific proteins,

166 between SMG6-dependent and SMG6-independent NMD pathways.

167 at disrupt the SMG7-UPF1 complex and inhibit NMD.

168 isense morpholino oligonucleotides inhibited NMD and rescued the functional expression of a third LQT

169 , also improves survival, whereas inhibiting NMD prevents rescue by hUPF1, suggesting that hUPF1 acts

170 Interestingly, NMD is also linked to immune responses at another level:

171 on of a dominant-interfering form of the key NMD factor UPF1.

172 rks genetic screen identifies multiple known NMD factors and numerous human candidate genes, providin

173 ome-wide analyses of UPF1 binding locations, NMD-regulated gene expression, and translation in murine

174 linical heterogeneity that exists among many NMDs and by limited knowledge about disease-specific car

175 nts are then stabilized by caffeine-mediated NMD inhibition, breaking the normal negative feedback lo

176 monstrate an essential role of UPF2-mediated NMD in prepubertal SC development and male fertility.

177 to IR also occurs when other genes mediating NMD are mutated.

178 mutations that are predicted to elicit NMD (NMD-elicit).

179 s as genuine, preserving both the ability of NMD to accurately detect aberrant mRNAs and the capacity

180 1, leading to indiscriminate accumulation of NMD complexes on both NMD target and non-target mRNAs.

181 From yeasts to humans, activation of NMD requires the function of the three conserved Upf fac

182 e mRNP remodelling, leading to activation of NMD.

183 veloped a method of in vivo amplification of NMD reporter fluorescence (Fireworks) that enables CRISP

184 Notably, this increased burden of NMD, INIT and splice variants was more pronounced in a s

185 ion of hUPF2, another essential component of NMD, also improves survival, whereas inhibiting NMD prev

186 Although the conservation of NMD exons in RBPs frequently extends into lower vertebra

187 e initial targeting and final degradation of NMD-susceptible mRNAs.

188 Indeed, loss or depletion of NMD factors have been shown to disrupt developmental eve

189 involvement, highlighting unique features of NMD-associated myocardial disease that require clinician

190 Unexpectedly, a second group of NMD exons reside in genes encoding chromatin regulators.

191 esence of unique features - key hallmarks of NMD targets in the p53beta transcript, which was further

192 The inhibition of NMD and upregulation of SLC7A11 augments intracellular c

193 elf degraded by NMD, such that inhibition of NMD by DUX4 protein stabilizes DUX4 mRNA through a doubl

194 Here we demonstrate that the inhibition of NMD by various cellular stresses leads to the stabilizat

195 the growing evidence that the inhibition of NMD is an adaptive response.

196 Accordingly, the inhibition of NMD protects cells against oxidative stress via SLC7A11

197 tabilized by caffeine-mediated inhibition of NMD, down-regulation of NMD by a genetic approach was no

198 lasmic reticulum also leads to inhibition of NMD.

199 re of cells to a small-molecule inhibitor of NMD, NMDI-1, and the chemotherapeutic doxorubicin leads

200 ouabain and digoxin, as potent inhibitors of NMD.

201 erturb NMD, leading to upregulated levels of NMD substrate mRNAs.

202 strate this technique on the localization of NMD-insensitive splice variants of two Arabidopsis thali

203 While loss of NMD is tolerated, loss of hUPF1 induces a DNA damage res

204 d RAD57 Finally, we demonstrate that loss of NMD results in an increase in recombination rates and re

205 However, the majority of NMD factors were first discovered in model organisms and

206 Here, we will focus on the mechanism of NMD with an emphasis on the role of RNA helicases in the

207 understanding of the molecular mechanisms of NMD in several model systems and discuss recent experime

208 Here, we report a gene-specific method of NMD inhibition using antisense oligonucleotides (ASOs) a

209 In addition, two modulators of NMD-translation and termination codon-proximal poly(A) b

210 of diverse function are under the purview of NMD.

211 diated inhibition of NMD, down-regulation of NMD by a genetic approach was not sufficient to reproduc

212 , through the stress-inhibited regulation of NMD, and add to the growing evidence that the inhibition

213 intracellular calcium as a key regulator of NMD and has implications for exploiting NMD in the treat

214 he roles of Upf1, the principal regulator of NMD, in the initial targeting and final degradation of N

215 F1), an RNA helicase and master regulator of NMD, in these disorders.

216 Despite the critical role of NMD at the cellular level, our knowledge about the conse

217 The central role of NMD in the control of gene expression requires the exist

218 Studies of NMD helped lead us to the therapeutic concept of treatin

219 rameshift mutations are potential targets of NMD.

220 Transcriptomes of NMD-impaired and heat-stressed plants shared a set of re

221 To expedite the molecular diagnosis of NMDs, we designed and validated several next generation

222 The clinical and genetic heterogeneities of NMDs make disease diagnosis complicated and expensive, o

223 tunities by targeting tumour dependencies on NMD-elicit mutations.

224 Cardiac glycoside-mediated effects on NMD are dependent on binding and inhibiting the sodium-p

225 p-UPF1 is enriched on NMD target 3' untranslated regions (UTRs) along with sup

226 required to best inform future guidelines on NMD-specific cardiovascular health risks, treatments, an

227 UPF1 undergoes regulated phosphorylation on NMD targets, providing a binding platform for mRNA degra

228 were not consistently associated with FMD or NMD.

229 RNA degradation factors and retained partial NMD activity.

230 Since partial NMD attenuation can potentially enhance nonsense suppres

231 utations alter UPF1 RNA splicing and perturb NMD, leading to upregulated levels of NMD substrate mRNA

232 As expected, pharmacologic NMD inhibition disrupted SMG7-UPF1 interactions.

233 in cells with PTC-mutated p53, pharmacologic NMD inhibition combined with a PTC "read-through" drug l

234 serve as proof-of-concept that pharmacologic NMD inhibitors can restore mRNA integrity in the presenc

235 overed that UPF3A acts primarily as a potent NMD inhibitor that stabilizes hundreds of transcripts.

236 Here we develop an algorithm to predict NMD and apply it on somatic mutations reported in The Ca

237 In conclusion, preoperative NMD and FMD positively associated with changes in 6-week

238 (NMD) machinery, is associated with profound NMD inhibition, resulting in global accumulation of RNAs

239 ating that the UPF1 mutations led to reduced NMD magnitude.

240 el p38alpha-dependent pathway that regulates NMD activity in response to persistent DNA damage, which

241 statement, we provide background on several NMDs in which there is cardiac involvement, highlighting

242 Indeed, slowing NMD by inhibiting late-acting factors triggers UPF1 hype

243 We discover cancer-specific NMD-elicit signatures in TSGs and cancer-associated gene

244 erapies, better definition of human-specific NMD is required.

245 ipulating splicing components, we found that NMD activities are crucial to control p53beta levels und

246 We found that NMD comprehensive panel testing has a 3-fold greater dia

247 ate specific DNA repair proteins and/or that NMD inactivation may lead to aberrant mRNAs leading to s

248 We propose that NMD-mediated RNA surveillance is a crucial quality contr

249 Here we show that NMD mediates longevity in C. elegans strains with mutati

250 We identify 3100 new Alu-exons and show that NMD more efficiently recognises transcripts with Alu-exo

251 known to induce DSBs, further supports that NMD pathway mutants are defective in DSB repair.

252 The NMD exons were regulated by seizures, which also induced

253 es at another level: mutations affecting the NMD or RNA exosome machineries cause chronic activation

254 ent cause of human genetic diseases, and the NMD pathway is known to modulate disease severity.

255 dulates a functional interaction between the NMD machinery and terminating ribosomes necessary for ta

256 F3B is involved in the crosstalk between the NMD machinery and the PTC-bound ribosome, a central mech

257 The molecular link between the NMD pathway and IMTs has implications for the diagnosis

258 en bound near a stop codon, PTBP1 blocks the NMD protein UPF1 from binding 3'UTRs.

259 gain variant predicted to be degraded by the NMD-pathway.

260 the nucleus, which allows them to escape the NMD machinery.

261 In humans, mutations in the NMD factor gene, UPF3B, cause intellectual disability (I

262 ing factors and their functional role in the NMD pathway.

263 ered by SMG1-mediated phosphorylation of the NMD factor UPF1.

264 Although some of the NMD machinery is conserved between kingdoms, little is k

265 A critical component of the NMD machinery is UPF1, an RNA helicase whose ATPase acti

266 in the SMG7 protein, a key component of the NMD mechanism, to identify compounds that disrupt the SM

267 enomics to determine the conservation of the NMD pathway across eukaryotic evolution.

268 Several mRNA targets of the NMD pathway were upregulated in IMT samples, indicating

269 dies have demonstrated the importance of the NMD pathway; however, evidence supporting its physiologi

270 variants deficient in various aspects of the NMD process in parallel with Forster resonance energy tr

271 n the study of the physiological role of the NMD response.

272 ted in vitro translation system to probe the NMD proteins for interaction with the termination appara

273 Our data demonstrate that the NMD and alternative splicing pathways regulate p53beta i

274 legislation as of 2014 submitted data to the NMD before and after law enactment.

275 or pediatric heart failure guidelines to the NMD population problematic.

276 ere disease than the PKD2 group, whereas the NMD group had a PKD2-like phenotype.

277 r, this mutant could still interact with the NMD and mRNA degradation factors and retained partial NM

278 These NMD exons are particularly enriched in RBPs including sp

279 Y2 is essential for the degradation of these NMD transcripts.

280 by hUPF1, suggesting that hUPF1 acts through NMD to enhance survival.

281 Thus, NMD provides a promising therapeutic target that would a

282 p-UPF1 binding to NMD target 3' UTRs is stabilized by SMG5 and SMG7.

283 ying splice variants that are insensitive to NMD; this led us to question the fate of these special R

284 l of sensitivity of a PTC-containing mRNA to NMD is multifactorial.

285 for the susceptibility of LQT2 mutations to NMD and posits that the majority of reported LQT2 nonsen

286 rrelates with 3'UTR length and resistance to NMD.

287 but the exons generally remain sensitive to NMD.

288 matic protein previously shown to have trace NMD activity.

289 diated decay in the majority of transcripts (NMD) (OR = 1.98, P = 0.02).

290 erstanding the molecular events that trigger NMD can facilitate strategic targeting of genes via CRIS

291 , we found that FRY2/CPL1 interacts with two NMD factors, eIF4AIII and UPF3, and is involved in the d

292 d the intriguing possibility of undiscovered NMD regulatory pathways.

293 ction is dependent on SMG6 and the universal NMD factor UPF1.

294 Several of these compounds upregulated NMD-targeted mRNAs at nanomolar concentrations, with min

295 These upregulated NMD targets included NIK mRNA, which encodes a potent ac

296 gene (NMD-associated) tests with the various NMD NGS panel tests, we analyzed data from all clinical

297 s frequently extends into lower vertebrates, NMD exons in chromatin regulators are introduced later i

298 es the cell survival defects associated with NMD knockdown.

299 stomach adenocarcinomas are associated with NMD-elicit mutations of the translation initiators LARP4

300 liced transcripts and 5'-extended mRNAs with NMD-eliciting features accumulated in the fry2-1 mutant,