ライフサイエンスコーパス: paraspeckle

1 involved in the assembly of Cajal bodies and paraspeckles.

2 edited, consistent with a structural role in paraspeckles.

3 ression results in the disruption of nuclear paraspeckles.

4 tial structural/organizational components of paraspeckles.

5 stributed in nuclei and is also localized to paraspeckles.

6 eckles are larger (>1 mum) than conventional paraspeckles.

7 1 core, and regulates the size and number of paraspeckles.

8 ockdown reduces the number and size of AGGF1-paraspeckles.

9 to the formation, structure, and function of paraspeckles.

10 _2 co-localize in 20.58% of NEAT1_2-positive paraspeckles.

11 mechanism underlying the formation of AGGF1-paraspeckles.

12 no known intersection of MUC1 with NEAT1 or paraspeckles.

13 inhibitors as potent negative modulators of paraspeckles.

14 AP2L, alleviating their inhibitory effect on paraspeckles.

15 action of non-structural RNA components with paraspeckles.

16 nucleus, where hLincRNA-p21 colocalizes with paraspeckles.

17 ed to be components of nuclear bodies called paraspeckles.

18 asm and retained in subnuclear bodies called paraspeckles.

19 n turn affecting the organization of nuclear paraspeckles.

20 d cells, and FUS deficiency leads to loss of paraspeckles.

21 nuclear bodies (38), nuclear speckles (27), paraspeckles (24), Cajal bodies (17), Sam68 nuclear bodi

22 ue, Hennig et al. show that formation of the paraspeckle, a nuclear body that regulates gene expressi

23 previously been shown to localize to nuclear paraspeckles, a structure implicated in retaining unspli

24 addition, in the absence of Neat1-nucleated paraspeckles, a subset of Ctn RNA localizes to the perin

25 Furthermore, the formation of paraspeckles, after release from transcriptional inhibit

26 on/beta transcripts are localized to nuclear paraspeckles and directly interact with NONO.

27 NEAT1 in HeLa cells results both in loss of paraspeckles and in enhanced nucleocytoplasmic export of

28 While interaction of protein components of paraspeckles and Neat1 is understood, there is limited i

29 ults identify a special type of AGGF1-coated paraspeckles and provide important insights into the for

30 can be displaced by transfected PS-ASO from paraspeckles and rapidly degraded.

31 significant overlap between the proteomes of paraspeckles and SGs.

32 Paraspeckles and stress granules (SGs) are prototypical

33 that is an essential structural component of paraspeckles and the hypoxic induction of NEAT1 induces

34 between a stressed-induced nuclear body, the paraspeckle, and IRES-dependent translation.

35 red for its colocalization with NEAT1 RNA in paraspeckles, and biochemical analyses support that NEAT

36 the nucleolus, nuclear lamina, Cajal bodies, paraspeckles, and PML bodies.

37 d PSP1 alpha are all expressed in hESCs, but paraspeckles are absent and only appear upon differentia

38 Nuclear paraspeckles are built co-transcriptionally around a lon

39 AGGF1-paraspeckles are larger (>1 mum) than conventional paras

40 dies, nuclear speckles, Polycomb bodies, and paraspeckles are membraneless subnuclear organelles.

41 Paraspeckles are multifunction nuclear structures that s

42 Paraspeckles are nuclear bodies form around the long non

43 Paraspeckles are nuclear bodies formed by a set of speci

44 Paraspeckles are nuclear bodies formed on the NEAT1 lncR

45 Nuclear paraspeckles are paradigmatic examples of multidomain co

46 Paraspeckles are ribonucleoprotein granules assembled by

47 Paraspeckles are small membraneless subnuclear structure

48 Paraspeckles are sub-nuclear domains that are nucleated

49 One such nuclear body, paraspeckles, are comprised of multiple paraspeckle prot

50 t1, the scaffold of the nuclear compartment "paraspeckles," are reciprocal in pluripotent and differe

51 eat1, a noncoding RNA (ncRNA) constituent of paraspeckles, as a p53 target gene broadly induced by mo

52 Here, we investigated whether paraspeckles, as defined by NEAT1 localization, are mech

53 trate that PABPN1 and MATR3 are required for paraspeckles, as well as for adenosine to inosine (A to

54 localizes with the RNA/DNA helicase Dhx9 and paraspeckles; as well as GW/P-bodies in the cytoplasm.

55 Paraspeckle assembly and function depend on expression o

56 Enhancing paraspeckle assembly by MEN beta-associated RNA promotes

57 A prevailing model of paraspeckle assembly proposes that core proteins bind di

58 Paraspeckle assembly requires NEAT1 recruitment of the R

59 The long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) is involved in

60 The long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1), which forms t

61 led by NEAT1_2 lncRNA, an isoform of Nuclear Paraspeckle Assembly Transcript 1 (NEAT1).

62 transcription of long non-coding RNA nuclear paraspeckle assembly transcript1 and the abundance of pa

63 in of FUS function can trigger disruption of paraspeckle assembly, which may impair protective respon

64 uired to trigger and maintain stress-induced paraspeckle assembly.

65 with adenosine-to-inosine editing and is in paraspeckle-associated complexes containing the proteins

66 MUC4, and GCN4 RNAs and allows the study of paraspeckle-associated NEAT1 dynamics.

67 Such nuclear retention correlates with paraspeckle-associated protein complexes containing p54(

68 s uncorrelated with nuclear localization and paraspeckle association.

69 ted neuron-specific formation of NEAT1-based paraspeckles at the SN and demonstrated coincreases of N

70 ts, suggesting that oriPts interact with the paraspeckle-based innate antiviral immune pathway.

71 T1), which forms the backbone of subnuclear "paraspeckle" bodies, has been identified as a key geneti

72 ent cells, TDP-43 represses the formation of paraspeckles by enhancing the polyadenylated short isofo

73 n (RNP) granules such as stress granules and paraspeckles can either promote the formation of double-

74 gether, our results indicate that functional paraspeckles can form with short nucleic acids other tha

75 chromosomal regions and the NEAT1-containing paraspeckle compartment.

76 Purification of the paraspeckle complex from adipocytes further showed that

77 NA-binding protein PSPC1, a component of the paraspeckle complex, promotes adipogenesis in vitro and

78 PII) and other RNA-binding proteins, such as paraspeckle component 1 (PSPC1), ultimately driving the

79 ear export of these mRNAs by methylating the paraspeckle component p54(nrb), which reduces the bindin

80 the long non-coding RNA Neat1, an essential paraspeckle component, is a key translational regulator,

81 ts, and down-regulating synthesis of another paraspeckle component, the long noncoding RNA NEAT1, whi

82 neurodegenerative disorders, is an essential paraspeckle component.

83 distinct subnuclear locations, for example, paraspeckle condensates, where DBHS proteins bind to the

84 sing siRNA knockdowns, we show these labeled paraspeckles consist of GFP-NONO/endogenous SFPQ dimers

85 ssembly and suggests a role for disturbed SG-paraspeckle crosstalk in human disease.

86 nation microscopic analyses revealed that in paraspeckles, Ctn RNA partially co-localized with Neat1,

87 FPQ dimers and that GFP-NONO localization to paraspeckles depends on endogenous SFPQ.

88 ignals, Neat1, which normally resides in the paraspeckles, disassociates from these nuclear bodies an

89 Collectively, these results show that while paraspeckles do not influence nuclear retention of Ctn R

90 otein:protein interaction involving the NONA/paraspeckle domain, which is characteristic of the DBHS

91 the recruitment of IRES-containing mRNA into paraspeckle during hypoxia.

92 lain the complexity of both DBHS protein and paraspeckle dynamics through imaging and structural appr

93 expression increases paraspeckle number, and paraspeckles emanate exclusively from the NEAT1 transcri

94 evels, resulting in an increased assembly of paraspeckles foci both in vitro and in human skin tissue

95 However currently NEAT1_2/paraspeckle-focused translational research and drug disc

96 We highlight these virus-modified paraspeckles form adjacent to virus replication centres,

97 stigation into the role of G-quadruplexes in paraspeckle formation and function.

98 s and the hypoxic induction of NEAT1 induces paraspeckle formation in a manner that is dependent upon

99 FUS also regulates NEAT1 levels and paraspeckle formation in cultured cells, and FUS deficie

100 ly increased NEAT1_2, which enhanced nuclear paraspeckle formation in human glioma cells.

101 tural component of paraspeckles that induces paraspeckle formation, forms an outside rim of paraspeck

102 ing Neat1 expression in mice, which prevents paraspeckle formation, sensitized preneoplastic cells to

103 ly, SGs may sequester negative regulators of paraspeckle formation, such as UBAP2L, alleviating their

104 ing RNA NEAT1 in the first essential step in paraspeckle formation.

105 associate with NEAT1_2 and are necessary for paraspeckle formation.

106 the long noncoding RNA NEAT1, which inhibits paraspeckle formation.

107 ress NEAT1 transcription, leading to reduced paraspeckle formation.

108 numerous regulatory functions to the nuclear paraspeckle-forming long noncoding RNA, nuclear enriched

109 on FUS mutations might be expected to affect paraspeckle function in human diseases because mislocali

110 Paraspeckle function is yet to be fully elucidated but h

111 together with PABPN1 is required for normal paraspeckle function.

112 Dysregulation of NEAT1_2/paraspeckles has been linked to multiple human diseases

113 We further show that paraspeckle hyperassembly is typical for cells subjected

114 ancer cell lines and observed an increase in paraspeckles in cells cultured on soft (3 kPa) hydrogels

115 SN and demonstrated coincreases of NEAT1 and paraspeckles in cultured cells under paraquat (PQ)-induc

116 lication stress, stimulated the formation of paraspeckles in mouse and human cells.

117 nd further substantiates a critical role for paraspeckles in the mechanism of action of Rev.

118 s granules in the cytoplasm and nucleoli and paraspeckles in the nucleus.

119 cts with p54nrb/NONO, a major constituent of paraspeckles, in an RNA-dependent manner and responds in

120 b was observed in canonical NEAT1-containing paraspeckles, in perinucleolar caps upon transcriptional

121 that, in pituitary cells, all components of paraspeckles including four major proteins and Neat1 dis

122 aspeckle number and size, we investigate how paraspeckles influence the nuclear organization of their

123 NEAT1 RNA, a long noncoding RNA required for paraspeckle integrity, abolished the ability of overexpr

124 dicating the dependence of RBM14 function on paraspeckle integrity.

125 ent triggers the translocation of CPSF6 from paraspeckles into nuclear speckles forming puncta-like s

126 bility between core and shell proteins order paraspeckle layers.

127 The induced formation of paraspeckle-like and filament structures occurred in mou

128 ecognition motif-like domain (RRM-L), a NONA/paraspeckle-like domain (NOPS-L), and extended alpha-hel

129 s can serve as seeding molecules to assemble paraspeckle-like foci in the absence of NEAT1 RNA.

130 ization of Ctn RNA, where it formed enlarged paraspeckle-like foci.

131 nscriptional inhibition, and importantly, in paraspeckle-like or filament structures lacking NEAT1 RN

132 terized the composition of affinity-purified paraspeckle-like structures and found a significant over

133 o paraspeckle-like structures, implying that paraspeckle-like structures assembled on PS-ASOs are fun

134 hologically normal and apparently functional paraspeckle-like structures containing no NEAT1 RNA.

135 raspeckles, was also observed to localize to paraspeckle-like structures, implying that paraspeckle-l

136 t1, and displayed a more heterogeneous intra-paraspeckle localization.

137 reactivation resulted in increased number of paraspeckle-localized Ctn RNA foci.

138 nuclear structures and co-localizes with the paraspeckle marker p54NRB/NONO, suggesting a role in tra

139 l extensive interactions with disease-linked paraspeckle markers and a specific set of pre-mRNA splic

140 These results suggest that paraspeckles may potentially form through self-associati

141 We thus propose that paraspeckles may prove of use as mechanosensors in cance

142 AT1 serves as a scaffold for the assembly of paraspeckles, membraneless nuclear organelles involved i

143 mmon lncRNA target with downstream impact on paraspeckle morphology and function.

144 mouse model of OPMD and demonstrate altered paraspeckle morphology in the presence of endogenous lev

145 1 is an essential architectural component of paraspeckle nuclear bodies, whose pathophysiological rel

146 that we show are completely coincident with paraspeckles, nuclear domains implicated in mRNA nuclear

147 Here, by varying paraspeckle number and size, we investigate how paraspec

148 sion of PSP1, NEAT1 overexpression increases paraspeckle number, and paraspeckles emanate exclusively

149 establishes a key genetic link between NEAT1 paraspeckles, p53 biology and tumorigenesis and identifi

150 ydrogels of extreme stiffnesses, we measured paraspeckle parameters in several cancer cell lines and

151 ontaining octamer-binding protein (NONO) and paraspeckle protein component 1 (PSPC1), proteins capabl

152 of Neat1, Ctn RNA continues to interact with paraspeckle protein NonO to form residual nuclear foci.

153 the absence of nucleolar mislocalization of paraspeckle protein P54nrb, ablation of P21 mRNA elevati

154 nalyses of representative RBPs show that the paraspeckle protein PSPC1 inhibits the RNA-induced prema

155 Further, the multifunctional paraspeckle protein, NONO, was found to bind to oriPt tr

156 ody, paraspeckles, are comprised of multiple paraspeckle proteins (PSPs) built around the architectur

157 share structural and functional homology to paraspeckle proteins comprising an RNA-recognition motif

158 is (ALS)-linked FUS variants sequester other paraspeckle proteins into aggregates formed in cultured

159 In addition, paraspeckle proteins p54(nrb) and PSPC1 as well as nucle

160 esting that it controls sequestration of the paraspeckle proteins PSP1 and p54, factors linked to A-I

161 manner and responds in the same way as other paraspeckle proteins to alterations in cellular homeosta

162 ntisense oligonucleotides (ASOs) can recruit paraspeckle proteins to form morphologically normal and

163 ow that RNase H1-dependent delocalization of paraspeckle proteins to nucleoli is an early event in PS

164 PS-ASOs can associate with paraspeckle proteins, including P54nrb, PSF, PSPC1 and h

165 l analyses support that NEAT1 RNA binds with paraspeckle proteins.

166 neural associated genes by interacting with paraspeckle proteins.

167 -complexity prion-like domains (PLDs) within paraspeckle proteins.

168 ns as an essential structural determinant of paraspeckles, providing a precedent for a ncRNA as the f

169 els, suggestive of mechanomemory upstream of paraspeckle regulation.

170 l that PSP sequestration into virus-modified paraspeckles result in increased genome instability duri

171 Conversely, paraspeckles sequester TDP-43 and other RBPs from mRNAs

172 transcript with a key role in regulation of paraspeckle size and number.

173 demonstrated that RBM14, a protein found in paraspeckle structures in the nucleus, is involved in HI

174 The tools we describe herein should boost paraspeckle studies and help guide the search, validatio

175 l emanating from either end of the dimer for paraspeckle subnuclear body formation.

176 oncoding RNA NEAT1 (Menepsilon/beta) to form paraspeckles, subnuclear bodies that alter gene expressi

177 Depletion of NEAT1 RNA via RNAi eradicates paraspeckles, suggesting that it controls sequestration

178 ns nuclear-retained in the absence of intact paraspeckles, suggesting that they do not regulate nucle

179 arch, validation and optimization of NEAT1_2/paraspeckle-targeted small molecules.

180 This study shows that paraspeckles, thanks to their circadian expression, cont

181 MUC1-C in the regulation of NEAT1, RBPs, and paraspeckles that has been co-opted in promoting cancer

182 a key regulatory and structural component of paraspeckles that induces paraspeckle formation, forms a

183 Paraspeckle thus appears as a platform to recruit IRES-c

184 Concomitant with increase in number of paraspeckles, transcriptional reactivation resulted in i

185 export of transcripts containing IRAlus from paraspeckles under certain cellular stresses, such as po

186 RNA reported to be functionally retained in paraspeckles, was also observed to localize to paraspeck

187 etention of the egfp mRNA that was lost when paraspeckles were disrupted whereas insertion of a singl

188 3 NBs are partially colocalized with nuclear paraspeckles, whose scaffolding lncRNA NEAT1 is dramatic

189 V) drives formation of structurally distinct paraspeckles with a dramatically increased size and alte

190 tructured illumination microscopy, revealing paraspeckles with dynamic, twisted elongated structures.

191 completely cleared from nuclear speckles and paraspeckles within 2 h.

192 le assembly transcript1 and the abundance of paraspeckles within iPSC-ITGA6(+) cells.

193 raspeckle formation, forms an outside rim of paraspeckles, wraps around the NONO/PSF/PSPC1/NEAT1 core