ライフサイエンスコーパス: multimeric

1 Jun is a highly conserved member of the multimeric activator protein 1 transcription factor comp

2 , Dronc, in fruit flies, is facilitated by a multimeric adaptor complex known as the apoptosome.

3 Multimeric adaptors are broadly involved in vesicle-medi

4 Purified high-molecular multimeric adiponectin similarly accumulated intracellul

5 ll pDCs are intrinsically more responsive to multimeric agonist of TLR9 and constitutively secrete ty

6 used native polcalcin dimers and engineered multimeric allergens to test the effects of affinity and

7 a-synuclein that ranges from a physiological multimeric, alpha-helical, and membrane-bound species th

8 integrity markers, and soluble monomeric and multimeric amyloid-beta and tau species were measured.

9 d 807 causes the C region to form aberrantly multimeric and aggregated complexes with an unstable sec

10 At high concentrations, the proteins are multimeric and dynamically interact with RNA in an RNA l

11 ion, gel filtration chromatography separated multimeric and monomeric forms of wild type and mutant h

12 The Nipah virus phosphoprotein (P) is multimeric and tethers the viral polymerase to the nucle

13 Tie2 is regulated directly by the multimeric angiopoietin (Ang) ligands, with Ang1 being i

14 2 and CD20 positive cancer cells, as well as multimeric antibody fragments with enhanced activity.

15 Multimeric antigen display and high overall valency are

16 eted cross-linking indicates that it forms a multimeric array.

17 ncies among multiple donors and acceptors in multimeric arrays has waited for further testing.

18 nome structure and gene silencing by forming multimeric assemblages to topologically entrap and progr

19 etermine the characteristics of the distinct multimeric assemblies - a flexuous, helical rod or a loo

20 ets and potentially other proteins that form multimeric assemblies and fibrils on membranes.

21 ort that oligomerization of PrPSc into small multimeric assemblies appears to be a critical biophysic

22 Consistent with the observed MORC-1 multimeric assemblies, MORC-1 forms nuclear puncta in ce

23 In multimeric assemblies, the controllable motors walk proc

24 as under nonreducing conditions it presented multimeric assembly forms.

25 ts are several enzymes for which the correct multimeric assembly is crucial to their activity, such a

26 orthogonal arrays, linking epitope-dependent multimeric assembly with enhanced C1q binding and activa

27 its cognate effector, SopB, implying a novel multimeric association for chaperone/effector complexes

28 to a central spine, presumably facilitating multimeric attachment to the cell receptor.

29 nked glycan has a similarly critical role in multimeric, avidly binding Fcs, is unknown.

30 PFO forms a multimeric barrel with many TM segments.

31 s thread-like shape exposes its monomers for multimeric binding to platelets and subendothelium and l

32 Proteolysis of the multimeric blood coagulation protein von Willebrand Fact

33 Von Willebrand factor (VWF), a large multimeric blood protein, senses changes in shear stress

34 Physiological concentrations of multimeric but not monomeric cochlin reduce TREK-1 curre

35 ic state as being monomeric, dimeric, and/or multimeric, but the native cellular stoichiometry has re

36 In multimeric cell-surface receptors, the conformational ch

37 c region in CESA oligomerization to form the multimeric cellulose-synthesis complexes that are charac

38 TRPM1 likely forms a multimeric channel complex, although almost nothing is k

39 Secretins form multimeric channels across the outer membrane of Gram-ne

40 gative mutations in other disease-associated multimeric channels, we developed a generalizable comput

41 ntly influence subunit stoichiometry to form multimeric channels.

42 lized regulatory mechanism for other related multimeric channels.

43 iral reverse genetic system and introduced a multimeric clone into the laboratory model plant Nicotia

44 recise excision of the viral genome from the multimeric clones in inoculated leaves.

45 Agroinoculation of multimeric clones of the genomic DNA of three ToLDeV gen

46 Pourbaix diagrams with full consideration of multimeric cluster speciation from computations.

47 APLP1 oligomerization and forced APLP1 into multimeric clusters at the plasma membrane consistent wi

48 metastable but also thermodynamically stable multimeric clusters in aqueous solutions.

49 s demonstrate that high shear stress-induced multimeric cochlin produces a qualitatively different in

50 eased amount of HSP47 bound to monomeric and multimeric collagen molecules.

51 while no changes were observed for a larger multimeric complex (Concanavalin A).

52 omeodomain (HD) transcription factors form a multimeric complex and assign neuronal subtype identitie

53 containing the WDXNWD motif dissociates the multimeric complex and reduces but does not fully abolis

54 Formation of a multimeric complex between C4-S and pro-CatK has been sp

55 -selection method that is applicable for any multimeric complex by investigating the stoichiometry of

56 A recent study has identified a new multimeric complex called retriever that is essential fo

57 is study, we demonstrate that CTLA-4 forms a multimeric complex comprised of TRIM and related LAX tha

58 phaSuFc complex, also known as ALT-803, is a multimeric complex constructed by fusing IL-15N72D.IL-15

59 ge assembly of splicing regulators (LASR), a multimeric complex containing the proteins hnRNP M, hnRN

60 ed at opposite sides of the protein allowing multimeric complex formation previously shown in ASC PYD

61 DM1 and DM2d each resides in a multimeric complex in the absence of signaling, with the

62 units and their positions within the overall multimeric complex is key to understanding the molecular

63 ophilic and thermostable enzyme comprising a multimeric complex of the alpha(2) beta(2) or (alpha(2)

64 f the viral Rev adapter protein that forms a multimeric complex on these mRNAs prior to recruiting hC

65 rimental evidence for secretion of an intact multimeric complex requiring a signal formed by both mem

66 e.g., tubulin and actin) as a membrane-bound multimeric complex that favors p35 binding to Cdk5 and c

67 We conclude that Raa7 is a component of a multimeric complex that is required for trans-splicing o

68 s, we could demonstrate that AtALMT9 forms a multimeric complex that is supposedly composed of four s

69 Our results suggest the formation of a multimeric complex, dependent on a conserved cysteine at

70 roduct p100, transitions from a monomer to a multimeric complex, it may compete with and inhibit p100

71 tional criteria, for example membership of a multimeric complex, participation in a metabolic or sign

72 also affect stability and disassembly of the multimeric complex.

73 emonstrate that MPC is a hetero-dimer, not a multimeric complex.

74 re dependent on the interactions of Hand2 in multimeric complexes and are independent of direct DNA b

75 in the WDXNWD motif abolish the formation of multimeric complexes and markedly reduce phosphatase act

76 these mutated proteins assembled into large multimeric complexes and, compared to CFHR5, bound damag

77 that via homophilic interactions ORF3 forms multimeric complexes associated with intracellular endop

78 Typically, these membrane proteins are multimeric complexes associating several homologous subu

79 zed by CESA proteins that are organized into multimeric complexes called CESA complexes, in the plant

80 We find that they assemble into multimeric complexes comprising three to eight proteins

81 iffusing molecules, are often organized into multimeric complexes forming clusters on the cell and or

82 we were able to demonstrate the formation of multimeric complexes in live cells.

83 The assembly of large multimeric complexes in the crowded cytoplasm is challen

84 contributes to the assembly and function of multimeric complexes is an important question with impli

85 Although multimeric complexes of p100 (IkappaBdelta) are known to

86 t the surface of the cell membrane by large, multimeric complexes of synthase proteins.

87 s by combinatorial properties, acting within multimeric complexes to implement activation or repressi

88 The multimeric complexes were shown to reduce and prevent vi

89 e constructs can then be self-assembled into multimeric complexes with defined composition, valency,

90 N-terminal half of adenovirus e1a assembles multimeric complexes with host proteins that repress inn

91 Most proteins associate into multimeric complexes with specific architectures(1,2), w

92 homeodomain transcription factor that forms multimeric complexes with TALE and HOX proteins to regul

93 itions in ORF3 critical for its formation of multimeric complexes, ion channel activity, and, ultimat

94 f PGAM5, in which the assembly of PGAM5 into multimeric complexes, mediated by the WDXNWD motif, resu

95 copurifying with Cdk5/p35 in membrane-bound multimeric complexes.

96 o the structure determination of subunits of multimeric complexes.

97 is required for assembly of PGAM5 into large multimeric complexes.

98 tanding the assembly of other TPR-containing multimeric complexes.

99 not other regions, are in close proximity in multimeric complexes.

100 rtant for studying complicated MPs and their multimeric complexes.

101 together as stable, functionally integrated, multimeric complexes.

102 a coordinated manner, such as in pathways or multimeric complexes.

103 he binding constants of a ligand to a highly multimeric cooperative system, and thereby infer its all

104 Hemocyanins are multimeric copper-containing hemolymph proteins involved

105 in its integral capacity as a scaffold for a multimeric core complex.

106 tes ectopic skeletal elements resembling the multimeric covers of cartilaginous fishes.

107 omoting complex/cyclosome (APC/C) is a large multimeric cullin-RING E3 ubiquitin ligase that orchestr

108 The APC/C is an unusually large multimeric cullin-RING ligase.

109 Inflammasomes, multimeric cytosolic sensors of infection, are required

110 We expect that this enhanced multimeric de novo peptide design framework will find fu

111 proteins within the 26 S proteasome, a large multimeric degradation machine.

112 overcome these challenges with high-affinity multimeric designs.

113 KIR3DL2Fc pulled down multimeric, dimeric, and monomeric FHC from HLA-B27-expr

114 Multimeric discriminant functions combined with individu

115 ally engineered, to be used as platforms for multimeric display of foreign antigens.

116 biquitin chain assembly complex (LUBAC) is a multimeric E3 ligase that catalyses M1 or linear ubiquit

117 though the production of isolated domains of multimeric ectodomain proteins has proven difficult, we

118 r co-fractionation from lens extracts as one multimeric entity, alpha-crystallin.

119 To study the assembly of this multimeric enzyme complex consisting of membrane-integra

120 Multimeric enzyme complexes are ubiquitous in nature and

121 f chlorophyll biosynthesis is catalyzed by a multimeric enzyme, magnesium chelatase, the subunit I of

122 ther, the trend exists in both monomeric and multimeric enzymes and irrespective of enzyme size and/o

123 Our study establishes the principle that multimeric enzymes can exploit this cooperativity withou

124 ive approach to identify allosteric sites of multimeric enzymes in general.

125 Here we show that the multimeric ER proteins erlins-1 and -2 are additional SR

126 eta class of methyltransferases has a unique multimeric feature, forming either homo- or hetero-dimer

127 resulted in the formation of unusually large multimeric FHR complexes that exhibited increased avidit

128 d to increased levels of an overoxidized and multimeric form of Prdx-1 with activity as a molecular c

129 in cytosol to a physiologically functional, multimeric form upon membrane binding, and show that onl

130 its antiviral activity in a monomeric and/or multimeric form.

131 e plasma of patients revealed a reduction of multimeric forms and a reduced ability to bind the natur

132 nding to an isolated M-CAT-like DNA element, multimeric forms are deficient for cooperative binding t

133 trimer with three Fabs bound and two further multimeric forms comprising the destabilized spike attac

134 Using this mechanistic insight, we designed multimeric forms of anti-CD40 mAb with intrinsic Fcgamma

135 caused a reduction in antibody reactivity to multimeric forms of parvalbumins for most bony fish, a c

136 Prions are composed of misfolded and multimeric forms of the normal cellular prion protein (P

137 s were accurately assembled, including novel multimeric forms of the Y. pestis virulence plasmid, pPC

138 plasma metalloproteinase that cleaves large multimeric forms of von Willebrand factor (VWF) to small

139 aracter, making it prone to aggregation into multimeric forms.

140 Multimeric fragment crystallizable (Fc) regions and Fc-f

141 gle x-ray scattering in contrast to reported multimeric fucosidases.

142 The multimeric function, which consisted of the Zernike fitt

143 complexity is introduced in differentiating multimeric G-quadruplexes over monomeric species, which

144 MPQ-1 shifted the conformational ensemble of multimeric G-quadruplexes towards (3+1) hybrid-2 topolog

145 tion of potassium current was also seen with multimeric G85R SOD1YFP of approximately 300 kDa or >300

146 e mutations in GBMs to be recruitment of the multimeric GA-binding protein (GABP) transcription facto

147 f Gal80 in light of the evidence pointing to multimeric Gal80 as the form required to inhibit Gal4.

148 from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication.

149 that polymerase-helicase attachment promotes multimeric gel-like Poltheta complexes that facilitate D

150 aracterization of the primary structure of a multimeric glycoprotein in a single analysis by capillar

151 von Willebrand factor (VWF) is a large multimeric glycoprotein that mediates the attachment of

152 The large multimeric glycoprotein von Willebrand Factor (VWF) play

153 The large multimeric glyocoprotein von Willebrand factor (VWF) is

154 , a general prerequisite for the assembly of multimeric H(+)-translocating enzymes.

155 Inflammasomes are multimeric heterogeneous mega-Dalton protein complexes t

156 een immunized with a multicomponent vaccine (multimeric HIV-1 gp160, HIV-1 Tat, and SIV Gag-Pol parti

157 l tendency of each clone to form dimeric and multimeric immune complexes.

158 cellular FcgammaRs occurring in the form of multimeric immune complexes.

159 A multimeric immunogen based on the founder MPER activated

160 Upon activation, NLRP3 assembles a multimeric inflammasome complex comprising the adaptor A

161 activity or structure-specific disruption of multimeric interactions.

162 l propensity drives sites that are buried in multimeric interfaces to accumulate hydrophobic substitu

163 based single-molecule FRET measurements of a multimeric ion channel in a lipid bilayer have allowed u

164 ondrial Ca(2+) uniporter complex (MCUC) is a multimeric ion channel which, by tuning Ca(2+) influx in

165 Together, these results suggest that multimeric KhpA/B may function as a pleiotropic RNA chap

166 The function of this multimeric LASR complex has implications for deciphering

167 otently and specifically target a particular multimeric lectin for therapeutic interventions, especia

168 These findings indicate that multimeric ligands can significantly enhance conotoxin p

169 he characterization of industrial grade MDA, multimeric MDA species, and methylene diphenyl diisocyan

170 orulating Bacillus subtilis cells assemble a multimeric membrane complex connecting the mother cell a

171 gamma-Secretase complexes (GSECs) are multimeric membrane proteases involved in a variety of p

172 ive approach to extract the stoichiometry of multimeric membrane proteins in their native cellular en

173 ly at the presynaptic plasma membrane in its multimeric membrane-bound state, but not in its monomeri

174 e binding and oligomerization to form large, multimeric membrane-embedded complexes.

175 A multimeric model of the pore is presented based on these

176 symmetry aspects affecting the reactions of multimeric molecular structures.

177 rmal growth factor (EGF)-like molecule) is a multimeric, multimodular extracellular glycoprotein with

178 Recent development of genetically encoded multimeric nanoparticles (GEMs) has opened up study of t

179 cells, we tracked 40 nm genetically encoded multimeric nanoparticles (GEMs), whose sizes are commens

180 Bacillus subtilis ParB forms multimeric networks involving non-specific DNA binding l

181 ibe the synthesis and in vivo testing of two multimeric NIR-MR contrast agents that contain three Gd(

182 he various axonal proteins that comprise the multimeric nodal complex accumulate at this site.

183 egulation mechanisms shape the biogenesis of multimeric oxidative phosphorylation (OXPHOS) enzyme in

184 Multimeric oxo-hydroxo Al clusters function as models fo

185 most often in variants with a nearly normal multimeric pattern (type 2M).

186 ate that variations in von Willebrand factor multimeric pattern are highly dynamic, occurring within

187 Importantly, administration of soluble multimeric PD-L2 to mice with lethal malaria was suffici

188 Von Willebrand factor (VWF) is a multimeric plasma glycoprotein that is activated for hem

189 tween Stx and von Willebrand Factor (VWF), a multimeric plasma glycoprotein that mediates platelet ad

190 lebrand factor (VWF), an exceptionally large multimeric plasma glycoprotein, functions to initiate co

191 r activity 44 IU/dL; factor VIII 99%; normal multimeric plasma vWF pattern) was referred to our insti

192 ty using both a VWF A2 peptide substrate and multimeric plasma VWF.

193 s the synthesis and biological evaluation of multimeric polyamine derivatives as efficient PTS ligand

194 Collectively these multimeric polymerases ensure DNA replication proceeds a

195 e in NT4 peptides led to identification of a multimeric positively charged motif, which mediates inte

196 Meprins are multimeric proteases that are implicated in inflammatory

197 es, we produced at high levels in bacteria a multimeric protein (alpha11-88x8) fusing eight polypepti

198 net charge density and the size of resulting multimeric protein assemblies of narrow polydispersity.

199 The retromer complex is a multimeric protein complex involved in recycling protein

200 The retromer is a highly conserved multimeric protein complex present in all eukaryotic cel

201 The NLRP3 inflammasome is a multimeric protein complex that is assembled in response

202 n nuclear receptor that we show engages in a multimeric protein complex to regulate the transcription

203 Mechanistically, S18-2 formed a multimeric protein complex with prohibitin and the ring

204 help nascent polypeptides fold correctly and multimeric protein complexes assemble productively, whil

205 The spliceosome machinery is composed of multimeric protein complexes that generate a diverse rep

206 cule, which leads to the spatial assembly of multimeric protein complexes.

207 ature on the stability and structure of four multimeric protein complexes.

208 try with which monomers are arranged in many multimeric protein complexes.

209 Von Willebrand Factor (VWF) is a multimeric protein crucial for hemostasis.

210 The dynamic domain rearrangements of this multimeric protein have thwarted structural study of the

211 wever, understanding the cell cycle roles of multimeric protein phosphatases has been limited by the

212 transition that results in the creation of a multimeric protein pore.

213 ace, anchored in both bacterial membranes by multimeric protein rings.

214 t chemical and biological studies on natural multimeric protein structures, including fibers, rings,

215 PAH is a multidomain homo-multimeric protein whose conformation and multimerizatio

216 von Willebrand factor (VWF), a multimeric protein with a central role in hemostasis, ha

217 ity to control labeling of subunits within a multimeric protein with acceptor and donor fluorophores,

218 ins are considered to be two subunits of one multimeric protein, alpha-crystallin, within the ocular

219 As a secreted multimeric protein, CTRP11 forms disulfide-linked oligom

220 These results highlight the use of multimeric protein-polymer conjugates for their potentia

221 bind cooperatively to DNA and to form large multimeric protein/DNA fibers.

222 is shown that the method is compatible with multimeric proteins and those with post-translational mo

223 Soluble, recombinant multimeric proteins based on the HIV-1 env gene are curr

224 by its amino acid sequence, but how complex multimeric proteins fold and assemble into functional qu

225 The concerted transition model for multimeric proteins is a simple formulation for analyzin

226 icals, is especially useful for insoluble or multimeric proteins required for oral drug delivery.

227 Ion channels are dynamic multimeric proteins that often undergo multiple unsynchr

228 Cooperativity is a feature many multimeric proteins use to control activity.

229 s range of the device for analysis of larger multimeric proteins, all while maintaining the normal in

230 In cases of multimeric proteins, such allosteric regulation has ofte

231 ting distances up to 170 A to be accessed in multimeric proteins.

232 for producing individual domains of complex multimeric proteins.

233 the allosteric transitions of multidomain or multimeric proteins.

234 Our data suggest that the multimeric proteome rapidly responds to changes in hydra

235 distance measurements between spin-labels on multimeric protonated proteins using double electron-ele

236 ive, with the large GTPase Dynamin-3 and the multimeric PSD adaptor protein Homer1 as the two main pl

237 Intriguingly, one subfamily retained a multimeric quaternary structure and has small insertions

238 at optimal CDC was driven by the assembly of multimeric rAb platforms that increase multivalent C1q b

239 ed 20 different proteins, both monomeric and multimeric, ranging in mass from 2846 Da (melittin) to 1

240 ng of one or more molecules of a ligand to a multimeric receptor makes it more difficult for subseque

241 Negative cooperativity can make a multimeric receptor's response more graded than it would

242 sts that the mutated delta incorporates into multimeric receptors and reduces the overall forward tra

243 reveals that assembly of Pcdh isoforms into multimeric recognition units and the observed tolerance

244 gment of VWF, plasmin-cleaved dimers of VWF, multimeric recombinant VWF, and normal VWF plasma concen

245 Our experiments demonstrate that multimeric regulatory complexes feature a dynamic interp

246 of function might explain how other complex multimeric restriction enzymes act.

247 The anaphase-promoting complex (APC/C) is a multimeric RING E3 ubiquitin ligase that controls chromo

248 -related genes, in particular, components of multimeric RING E3 ubiquitin ligases including F-Box, SK

249 Multimeric, ring-shaped molecular motors rely on the coo

250 YscJ proteins form large multimeric rings that are the structural scaffolds for t

251 Within these multimeric RNAP-encoding Caudovirales (mReC), we find th

252 tric rolling circle mechanism to form linear multimeric RNAs.

253 of the antigen by combining antigens with a multimeric scaffold.

254 the Fab1 complex requires Vac14/ArPIKfyve, a multimeric scaffolding adaptor protein that coordinates

255 Members of a group of multimeric secretion pores that assemble independently o

256 roteins can be versatile building blocks for multimeric, self-assembling structures.

257 ate of number, size, and composition of such multimeric SHE particles in the cell.

258 CM304 increased the proportion of multimeric sigma1Rs, whereas (+)-pentazocine increased m

259 tion receptor signaling is the assembly of a multimeric signaling platform, termed the inflammasome,

260 nd form that is composed of an alpha-helical multimeric species that chaperones SNARE-complex assembl

261 assembles at the fork into a distribution of multimeric species, each encompassing a broad distributi

262 useful in the characterization of larger MDA multimeric species, industrial MDA mixtures, and methyle

263 low condensation, folding, and assembly into multimeric spheres of tunable well-defined size and low

264 of ssDNA in modulating the binding mode of a multimeric SSB protein and consequently, in generating t

265 Multimeric SSBs, such as the human mitochondrial SSB (Hm

266 We chemically construct multimeric standards to estimate the prebleaching probab

267 -TM helix proteins may link raft affinity to multimeric state and thus control the assembly of multim

268 bly of the transpososome and arises from the multimeric state of the transposase, mediated by a compe

269 e a unified dataset reporting the amount and multimeric state of VWF secreted from the constitutive,

270 our findings provide a mechanism wherein the multimeric states of both Mff and Drp1 regulate their co

271 Here, it is suggested that variation in the multimeric states of proteins can readily arise from sto

272 further insight into the different types of multimeric states that this protein can adopt, we genera

273 ze, store, and secrete von Willebrand factor multimeric strings and coagulation factor (F) VIII.

274 th inadequate cleavage by ADAMTS-13 of ULVWF multimeric strings secreted by/anchored to ECs (thrombot

275 and activated on EC-secreted/anchored ULVWF multimeric strings.

276 d to a protein, or surrounding subunits in a multimeric structure or assembly.

277 human IgG1 (IgG1-Fc) can be engineered into multimeric structures (hexa-Fcs) that bind their cognate

278 us which have been shown to crystallise into multimeric structures have been examined for their scaff

279 lassification algorithms can also be used on multimeric structures obtained using other high-resoluti

280 es of proteins is their common assembly into multimeric structures, usually homomers with even number

281 ing accurate prediction of protein folds and multimeric structures.

282 Most scaffolding nups are organized in two multimeric subcomplexes, the Nup84 or Y complex and the

283 We used an mAb and/or a multimeric synthetic sulfated sialoglycan ligand recogni

284 n) based on metrics that we have devised for multimeric systems.

285 The first stage uses a simulated multimeric template structure as input into the optimiza

286 meric state and thus control the assembly of multimeric TM complexes in rafts.

287 Since other multimeric trafficking adaptors operate in an analogous

288 ukemia (Scl or Tal1) protein forms part of a multimeric transcription factor complex required for nor

289 IM domain-binding protein 1 (LDB1) nucleates multimeric transcriptional complexes and establishes pro

290 cribed here are based on either monomeric or multimeric units harboring RNA aptamers as protein docki

291 ies for the controlled synthesis of extended multimeric units with tunable properties and the potenti

292 G assembly, and is exhibited broadly by homo-multimeric (valency >= 2) proteins across several cell t

293 to constantly release a soluble trimeric and multimeric variant of the known anti-cancer TNF-related

294 nd provides a scaffold for the assembly of a multimeric viral-cellular NEC.

295 Multimeric von Willebrand factor (VWF) is essential for

296 ccur in VWD variants of the A1 domain within multimeric VWF and provides strong support for VWF misfo

297 3-mediated proteolysis of peptidyl VWF73 and multimeric VWF are 3.5 muM and 45 muM, respectively.

298 presence of A1 domain structural disorder in multimeric VWF harboring type 2 VWD mutations.

299 e in local secondary structures of A1 within multimeric VWF.

300 p, about half of the expressed proteins were multimeric, with the efficiency of trans-splicing and ex