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1 RRE recognition triggers a crucial coil-to-helix transit
3 The precise secondary structure of the HIV-1 RRE has been controversial, since studies have reported
7 ation, the secondary structures of the HIV-2 RRE and two RNA folding precursors have been identified
8 nalysis collectively suggests that the HIV-2 RRE undergoes two conformational transitions before assu
11 cence titration assay revealed high-affinity RRE RNA binding by all 22 metal-chelate-Rev species, wit
12 c compounds, as a specific and high-affinity RRE-IIB binder which inhibits the interaction of the Rev
13 ssess whether BALF5 might be activated by an RRE-dependent mechanism, an Rta mutant (Rta K156A), defi
15 stem by an additional base pair, creating an RRE that was more responsive to lower concentrations of
17 t (Rta K156A), deficient for DNA binding and RRE activation but competent for Zp/Rp activation, was u
23 able to promote replication of the Rev- and RRE-defective HIV-1 in both human lymphoid cell lines an
24 (nucleocapsid) locally melts the TAR RNA and RRE-IIB RNA hairpins, whereas arginine-rich motif protei
29 In SSKH cells, Rev failed to activate both RRE-mediated reporter gene [chloramphenicol acetyltransf
32 also reflected at the levels of cytoplasmic RRE-chloramphenicol acetyltransferase mRNAs, indicating
34 t the first crystal structure of a Rev dimer-RRE complex, revealing a dramatic rearrangement of the R
35 nter in a protein and suggest that dinuclear RRE species, not mononuclear DNICs, may be the primary i
37 transactivation of reporters containing each RRE showed that their promoter strengths in a transient-
38 lectrophoretic mobility shift assays of each RRE demonstrated that the highly purified Rdbd protein d
39 ngth Ets-1 binds equivalently to BTE and EBS-RRE probes, while recombinant GABPalpha/beta preferentia
41 osslinking experiments with radiolabeled EBS-RRE and BTE oligonucleotides showed that these probes sp
42 ning GABP, we were able to show that the EBS-RRE preferentially binds Ets-1, while the BTE binds both
44 Ss contained in the RRE and BTE, we used EBS-RRE and BTE oligonucleotides in electrophoretic mobility
45 he level of relative replication efficiency (RRE) depends on the number and type of transcription fac
48 of virion (Rev) to the Rev response element (RRE) and subsequent oligomerization in a cooperative man
52 assembly of Rev on the Rev response element (RRE) is essential for the nuclear export of unspliced an
54 multiple sites in the Rev response element (RRE) of viral mRNA transcripts in nuclei of host cells,
55 NA containing either a Rev response element (RRE) or a Mason-Pfizer monkey virus (MPMV) constitutive
56 V-1 protein Rev on the Rev Response Element (RRE) regulates nuclear export of genomic viral RNA and p
57 been proposed for the Rev-response element (RRE) responsible for viral mRNA export, how it recruits
58 oop II region of HIV-1 Rev response element (RRE) RNA enhanced binding of HIV-1 Rev protein to the RR
59 n homooligomer and the Rev response element (RRE) RNA to mediate nuclear export of unspliced viral mR
61 al RNAs containing the Rev Response Element (RRE) through the Crm1 nuclear export pathway to the cyto
62 al Rev protein and the Rev response element (RRE), a structured element located in the Env region of
63 bunits assemble on the Rev Response Element (RRE), a structured region present in these RNAs, and dir
64 within viral RNA, the Rev response element (RRE), and escorts RRE-containing RNAs from the nucleus.
65 ral mRNAs encoding the Rev response element (RRE), thereby facilitating viral late gene expression.
66 virus (HIV) mRNAs, the Rev response element (RRE), to recruit the cellular nuclear export receptor Cr
67 transcripts harbor the Rev Response Element (RRE), which orchestrates the interaction with the Rev AR
68 or, unexpectedly, the Rev response element (RRE), which regulates the nuclear export of gRNAs and ot
69 P to mediate export of Rev response element (RRE)-containing human immunodeficiency virus (HIV) RNA,
71 ies with, HIV-1 Rev in Rev-response element (RRE)-mediated gene expression and virus replication.
76 hich we have named the Ras response element (RRE); whereas the response of multiple growth factors (F
79 is dependent on the Ras responsive element (RRE) binding protein (RREB1), which negatively regulates
80 interactions with an RTA-responsive element (RRE) could complement the loss of one RBPjkappa binding
82 interaction with the Rev responsive element (RRE) of HIV-1 mRNA has been studied by directly observin
83 viral elements, the Rev-responsive element (RRE) of the human immunodeficiency virus (HIV), and the
85 ions between the HIV Rev-responsive element (RRE) RNA and the HIV regulatory protein Rev, are crucial
87 munodeficiency virus Rev-responsive element (RRE) RNA by the Rev protein is an essential step in the
88 ind and activate the Rev-responsive element (RRE) RNA or heterologous MS2 phage operator RNA, we anal
90 otein that binds the Rev responsive element (RRE) within the env gene of the HIV-1 RNA genome, activa
91 ously reported 16-bp RTA-responsive element (RRE), and the same mutation also both reduced RTA-mediat
92 As opposed to HIV's Rev-responsive element (RRE), the Rex-responsive element (RxRE) is present in al
93 SNV) facilitates Rev/Rev-responsive element (RRE)-independent expression of intron-containing human i
95 uclear export element (Rev-response element [RRE]) used by HIV-1 and EIAV with the hepatitis B virus
100 e RNA motifs known as Rev response elements (RREs) is required for transport of unspliced and partial
102 a special focus on Ras responsive elements (RREs), the MAP kinases (Erks, p38 and JNK) and Ca2+-spec
103 sest relatives of Sam68, marginally enhanced RRE-mediated transactivation, while QK isoforms that are
106 l model of a Rev dimer bound to an essential RRE hairpin and to visualize the complete Rev-RRE RNP, d
107 s)(2)(NO)(4)], having a Roussin's red ester (RRE) formula, and that mononuclear DNICs account for onl
108 structurally related to Roussin's Red Ester (RRE, [Fe2 (NO)4 (Cys)2 ]) and Roussin's Black Salt (RBS,
109 eities in tempo (relative rate of evolution, RRE) and mode (selection pressure, Ka/Ks) in six organis
110 M10 resistance, which prompted us to examine RRE structure using a novel chemical probing strategy.
112 uction correlated with the failure to export RRE-containing CAT mRNA and unspliced viral mRNAs to the
117 mutants that preserved the Rev response for RRE RNA localized to the nuclei; those with poor or no R
121 constants and chemical reactivity toward HIV RRE RNA have been determined and evaluated in terms of r
123 d nuclear residence times and differences in RRE binding affinity may have compromised their activati
125 immunodeficiency virus type 1 (HIV-1) Rev in RRE (Rev response element)-mediated gene expression and
128 d the functional contributions of individual RRE domains and now report that several domains contribu
129 analysis showed strong enrichment for known RREs but little or no enrichment for Rp or Zp, suggestin
136 loops from HIV-1 Rev Response Element mRNA (RRE RNA) and ribosomal 16S A-site RNA (16S RNA) by metal
137 footprinting results and studies with mutant RRE sequences indicate that the internal loop of RRE is
138 ing within the internal purine-rich bulge of RRE-IIB in a manner analogous to what has been observed
140 viral Rev protein induces nuclear export of RRE-containing RNAs, as required for virus replication.
143 sequences indicate that the internal loop of RRE is required for specific binding of DB340 as with th
145 specific hydrogen bonding for recognition of RRE, shape recognition, through contact with the sugar-p
148 e the effects of these KH family proteins on RRE- and CTE (constitutive transport element of type-D r
149 t two classes of proflavine binding sites on RRE-IIB: a high-affinity site that competes with the Rev
150 s used to directly assess Rev "loading" onto RRE and its variants, indicating that this is unaffected
153 turally intronless genes, but not the CTE or RRE from intron-containing genes, significantly enhanced
157 ctly to the polyadenylated nuclear RNA (PAN) RRE motif, failed to bind to the RAP RRE and interfered
161 ory efficacy of proflavin on the Rev peptide-RRE binding, even in the presence of substantial levels
162 nsor for sensitively quantifying Rev peptide-RRE interaction and characterizing the potential inhibit
164 responsive element of the PAN promoter (pPAN RRE) was previously identified, and our data suggested d
166 , an extensive mutagenesis study on the pPAN RRE was carried out by using EMSAs and reporter assays.
167 ociation constant (K(d)) of Rdbd on the pPAN RRE was determined to be approximately 8 x 10(-9) M, sug
170 in the NOESY spectrum of the 2:1 proflavine.RRE-IIB complex indicate that the two proflavine molecul
171 ndicate that formation of the 2:1 proflavine.RRE-IIB complex stabilizes base pairing and stacking wit
172 ng interaction occurs with a 2:1 (proflavine:RRE-IIB) stoichiometry, and NOEs observed in the NOESY s
173 A (PAN) RRE motif, failed to bind to the RAP RRE and interfered with RRE-bound C/EBPalpha in EMSA exp
174 suggest that RTA transactivation of the RAP RRE is mediated by an interaction with DNA-bound C/EBPal
179 RE hairpin and to visualize the complete Rev-RRE RNP, demonstrating that RRE binding drives assembly
183 trajectories recorded during individual Rev-RRE assembly reactions has revealed the microscopic rate
184 assembly and dissociation of individual Rev-RRE complexes in the presence or absence of DDX1 were ob
187 rted in previous bulk kinetic studies of Rev-RRE association, indicating that oligomerization is an e
189 tering (SAXS) reveals two major steps of Rev-RRE complex formation, beginning with rapid Rev binding
192 or dominant-negative mutants suppressed Rev-RRE-function in the export of incompletely spliced HIV-1
197 el of activity throughout infection, the Rev-RRE system can fluctuate, presumably to control replicat
198 interface that enhances association with Rev-RRE and poises NES binding sites to interact with a Rev
202 m of the RRE promotes greater functional Rev/RRE activity compared to the four stem-loop counterpart.
205 -1 structural proteins in the absence of Rev/RRE is caused by inefficient accumulation of mRNA in the
211 Mechanistic studies indicated that the Rev/RRE-mediated inhibition did not involve either nuclear r
213 ) into a truncated form of the RRE sequence (RRE-IIB) allowed the binding of an arginine-rich peptide
214 uorescently labeled Rev monomers to a single RRE molecule was visualized, and the event frequencies a
218 are necessary and sufficient for substantial RRE function, provided they are joined by a flexible lin
219 dependent viral gag-pol mRNAs bearing tandem RREs (GP-2xRRE), rescue virus particle production in mur
221 their high-affinity binding to the targeted RRE mRNA following coupling to the Rev peptide, this cla
222 the complete Rev-RRE RNP, demonstrating that RRE binding drives assembly of Rev homooligomers into as
224 eins that can bind to HIV RNA containing the RRE in vivo but are unable to mediate the export of this
225 accounts for the specificity of Rev for the RRE and thus the specific recognition of the viral RNA.
230 However, two silent G->A mutations in the RRE (RRE61) confer RevM10 resistance, which prompted us
231 H3NE) that bind to the EBSs contained in the RRE and BTE, we used EBS-RRE and BTE oligonucleotides in
233 a high-affinity site in stem-loop IIB of the RRE and proceeds rapidly by addition of single Rev monom
234 stem, we demonstrated that the region of the RRE and TATA box constitutes an ORF50/Rta-dependent prom
235 partially spliced viral RNA; binding of the RRE by the viral Rev protein induces nuclear export of R
236 onstrate that the five stem-loop form of the RRE promotes greater functional Rev/RRE activity compare
237 nopurine (2-AP) into a truncated form of the RRE sequence (RRE-IIB) allowed the binding of an arginin
240 igh affinity for the Rev binding site on the RRE (K(d) <or= 10 nM), but few compounds have a high spe
242 by cooperative oligomerization of Rev on the RRE scaffold and utilizes both protein-protein and prote
243 in enhancement of Rev oligomerization on the RRE that is correlated with an RNA structural change wit
244 cate that Rev assembles cooperatively on the RRE via a series of symmetrical tail-to-tail and head-to
250 DX1 acts as an RNA chaperone, remodeling the RRE into a conformation that is pre-organized to bind th
257 mutants, we show that DDX1 acts through the RRE RNA to specifically accelerate the nucleation step o
260 DX21 was shown to enhance Rev binding to the RRE in a manner similar to that previously described for
262 nity binding of multiple Rev monomers to the RRE is achieved on a much faster timescale than reported
264 ggest that RSG 1.2 binds more tightly to the RRE sequence than Rev by forming more base-specific cont
265 show here that initial binding of Rev to the RRE triggers RNA tertiary structural changes, enabling f
266 t the binding of an ORF50/Rta protein to the RRE was essential for ori-Lyt-dependent DNA replication.
269 The structure supports a model in which the RRE utilizes the inherent plasticity of Rev subunit inte
270 ssay, both K-Rta and ORF59 interact with the RRE and C/EBPalpha binding motifs within oriLyt in cells
271 ripts in vivo, interacting directly with the RRE and Rev in vitro, and promoting Rev oligomerization
273 yt DNA through RTA, which interacts with the RRE, as well as K8, which binds to a cluster of C/EBP bi
276 We undertook a comparative study of the RREs of PAN RNA, ORF57, vIL-6, and Kpsn to understand ho
279 assess functional differences between these RRE 'conformers', we created conformationally locked mut
283 the stoichiometry of Rev peptide binding to RRE can be accurately determined by using this single-QD
284 competes with the Rev peptide for binding to RRE-IIB (K(D) approximately 0.1 +/- 0.05 microM) and a w
285 proflavine competes with Rev for binding to RRE-IIB by binding as a dimer to a single high-affinity
286 The results indicate that DB340 binds to RRE in a highly structured and cooperative complex at a
287 essential viral protein Rev, which binds to RRE RNA, to export their unspliced and partially spliced
288 de-RNA complexes of Rev and RSG 1.2 bound to RRE stem IIB have been solved and reveal gross structura
292 d that enables concurrent recognition of two RREs, thereby plausibly targeting tandem RREs present in
294 e N-terminal domain of SuiB adopts a typical RRE (RiPP recognition element) motif, which has been imp
295 ing replication, identify previously unknown RREs, such as one in BALF5p, and highlight the complexit
296 dramatic rearrangement of the Rev-dimer upon RRE binding through re-packing of its hydrophobic protei
297 end-diastolic diameter changes compared with RRE were -2.8 mm (-5.2 to -0.4 mm; P=0.02) in HIIT and -
298 the Rev and RSG 1.2 peptides in complex with RRE stem IIB have been simulated to better understand on
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