ライフサイエンスコーパス: CPSF

1 CPSF contains two functionally distinct modules: a cleav

2 CPSF-160 functions as an essential scaffold and preorgan

3 olyadenylation specificity factor subunit 3 (CPSF-73 or CPSF3).

4 These interactions are mediated by Fip1, a CPSF subunit characterized by high degree of intrinsic d

5 Mutations in the PIM can abolish CPSF formation, indicating that it is a crucial contact

6 nylation factors: symplekin, CstF64, and all CPSF subunits, including the endonuclease CPSF73.

7 nd 3' processing factors (DSIF, CstF-64, and CPSF-100) is also restored.

8 Both CPSF-73 and CPSF-100 contain two domains, a metallo-beta-lactamase d

9 , a factor involved in complex assembly, and CPSF-73, an endonuclease, as SUMO modification substrate

10 scaffold protein symplekin contacts CPEB and CPSF and helps them interact with Gld2, a poly(A) polyme

11 The first is symplekin, a CPEB and CPSF binding protein that serves as a scaffold upon whic

12 y(A) polymerase that is anchored to CPEB and CPSF even before polyadenylation begins.

13 de AAUAAA through associations with CPEB and CPSF, respectively.

14 t stimulates an interaction between CPEB and CPSF.

15 tor and also the recruitment of the CstF and CPSF (cleavage and polyadenylation specific factor) comp

16 ex with the polyadenylation factors CstF and CPSF.

17 RBFOX2 and CPSF/SYMPK then function together to regulate binding of

18 major sites of sumoylation in symplekin and CPSF-73 were determined and found to be highly conserved

19 ch we show interacts with both symplekin and CPSF-73, or by siRNA-mediated depletion of ubc9, the SUM

20 nt splicing and polyadenylation in vivo, and CPSF is brought to a promoter by the transcription facto

21 ion sites in a manner dependent on WDR82 and CPSF.

22 vo plant CPSF model in which the Arabidopsis CPSF possesses AtCPSF30, AtCPSF73-I, AtCPSF73-II, AtCPSF

23 ation experiments identified this protein as CPSF-73, a known component of the cleavage/polyadenylati

24 omplexes and impairs the interaction between CPSF and CSTF.

25 uggest a model where the interaction between CPSF and RNA-binding proteins, such as HNRNPA3, promotes

26 as it is associated with the AAUAAA-binding CPSF factor and can be co-immunoprecipitated with other

27 Both CPSF-73 and CPSF-100 contain two domains, a metallo-beta

28 his short motif to be bound directly by both CPSF-30 and WDR33.

29 ed here shows that complexes containing both CPSF and CPEB are present in extracts of X. laevis oocyt

30 This result implies that CLPS3 may bridge CPSF to the PCFS4 complex.

31 leavage of histone pre-mRNAs is catalyzed by CPSF-73 and requires the interaction of two U7 snRNP-ass

32 end of pre-mRNA and then defines cleavage by CPSF 73 and subsequent polyadenylation of its target mRN

33 litates recognition of the AAUAAA hexamer by CPSF.

34 l determinant of poly(A) site recognition by CPSF and may play a key role in poly(A) site definition.

35 er contribute to poly(A) site recognition by CPSF.

36 aining metallo-B-lactamase (MBL) and B-CASP (CPSF-Artemis-SNM1-Pso2) domains.

37 epletion experiments indicate that the Cdc73-CPSF-CstF complex is necessary for 3' mRNA processing in

38 hey include CPA's three main subunits, CFIm, CPSF, and CstF; lack essential splicing factors; and ass

39 time, that a member of the highly conserved CPSF 30K family is a nuclear and developmentally regulat

40 U1A to polyadenylation reactions containing CPSF, poly(A) polymerase, and a precleaved RNA substrate

41 A core CPSF complex comprising CPSF160, WDR33, CPSF30 and Fip1

42 on and translation in Xenopus oocytes (CPEB, CPSF, PAP, maskin, and IAK1, the murine homologue of Eg2

43 Cleavage and polyadenylation factor (CPF/CPSF) is a multi-protein complex essential for formation

44 Cleavage and polyadenylation factor (CPF/CPSF) is a multiprotein complex essential for mRNA 3' en

45 and polyadenylation specificity factor (CPF/CPSF).

46 bidopsis genome contains five genes encoding CPSF homologues (AtCPSF160, AtCPSF100, AtCPSF73-I, AtCPS

47 y and in mRNA 3'-end-processing endonuclease CPSF-73, containing metallo-beta-lactamase and beta-CASP

48 histone mRNAs by recruiting the endonuclease CPSF-73 to histone pre-mRNA.

49 cleavage site and recruits the endonuclease CPSF-73.

50 n the absence of the 3'-processing enhancer, CPSF binding and polyadenylation efficiency could be res

51 lyzed by the cleavage/polyadenylation factor CPSF-73.

52 g to the essential mRNA 3' processing factor CPSF.

53 vage and polyadenylation specificity factor (CPSF) 160 and 73 subunits and also the targeted pre-mRNA

54 vage and polyadenylation specificity factor (CPSF) and Aurora] also reside at synaptic sites of rat h

55 vage and polyadenylation specificity factor (CPSF) and cleavage stimulation factor (CstF) complexes t

56 vage and polyadenylation specificity factor (CPSF) and poly(A) polymerase (PAP) into an active cytopl

57 vage and polyadenylation specificity factor (CPSF) and SYMPK, are RBFOX2 cofactors for both inclusion

58 vage and polyadenylation specificity factor (CPSF) complex for 3'-end formation of mRNA, but it still

59 vage and polyadenylation specificity factor (CPSF) complex.

60 vage and polyadenylation specificity factor (CPSF) complex.

61 vage and Polyadenylation Specificity Factor (CPSF) complex.

62 vage and polyadenylation specificity factor (CPSF) complex.

63 vage and polyadenylation specificity factor (CPSF) complex.

64 vage and polyadenylation specificity factor (CPSF) constitutes the core of the 3' end processing mach

65 vage and polyadenylation specificity factor (CPSF) in humans, or cleavage and polyadenylation factor

66 vage and polyadenylation specificity factor (CPSF) in mammals.

67 vage and polyadenylation specificity factor (CPSF) is a complex one, encoding small (approximately 28

68 vage and polyadenylation specificity factor (CPSF) is an important multi-subunit component of the mRN

69 vage and polyadenylation specificity factor (CPSF) played a role in cytoplasmic polyadenylation.

70 vage and polyadenylation specificity factor (CPSF) subunits AtCPSF100 and AtCPSF160 were found.

71 cleavage-polyadenylation specificity factor (CPSF) to the upstream poly-adenylation sequence (AAUAAA)

72 vage and polyadenylation specificity factor (CPSF) with the core poly(A) site.

73 vage and polyadenylation specificity factor (CPSF), 3' cleavage of some cellular pre-mRNAs still occu

74 cleavage-polyadenylation specificity factor (CPSF), an activity needed for both cleavage and poly(A)

75 vage and polyadenylation specificity factor (CPSF), cleavage stimulation factor (CstF), and other pro

76 cleavage/polyadenylation-specificity factor (CPSF), cleavage-stimulation factor, two cleavage factors

77 vage and polyadenylation specificity factor (CPSF), cytoplasmic polyadenylation element binding prote

78 vage and polyadenylation specificity factor (CPSF), the factor responsible for recognition of AAUAAA,

79 vage and polyadenylation specificity factor (CPSF), the factor responsible for recognition of the AAU

80 vage and polyadenylation specificity factor (CPSF), two subunits of the cleavage stimulation factor (

81 vage and polyadenylation specificity factor (CPSF)-mediated 3' processing of nascent pre-mRNAs(10-15)

82 vage and polyadenylation specificity factor (CPSF).

83 vage and Polyadenylation Specificity Factor (CPSF).

84 vage and polyadenylation specificity factor (CPSF).

85 vage and polyadenylation specificity factor (CPSF).

86 cleavage/polyadenylation specificity factor (CPSF).

87 cleavage-polyadenylation specificity factor (CPSF).

88 vage and polyadenylation specificity factor (CPSF).

89 vage and polyadenylation specificity factor (CPSF).

90 vage and polyadenylation specificity factor (CPSF)73 (also known as CPSF3) is the endoribonuclease th

91 vage and polyadenylation specificity factor (CPSF-73) might be the endonuclease for this and related

92 vage and polyadenylation specificity factor (CPSF; CPF in yeast).

93 NA 3' end formation, the molecular basis for CPSF-AAUAAA interaction remains poorly defined.

94 the molecular architecture of the core human CPSF complex, identifying specific domains involved in i

95 efficient 3' endonuclease activity of human CPSF with purified proteins.

96 y structure of a quaternary complex of human CPSF-160, WDR33, CPSF-30, and an AAUAAA RNA at 3.4-A res

97 re we report the crystal structures of human CPSF-73 at 2.1 A resolution, complexed with zinc ions an

98 Here, we have produced recombinant human CPSF and CstF and examined these factors by electron mic

99 e in HSV-1-induced host shutoff and identify CPSF as an important factor that mediates regulation of

100 , indicating that it is a crucial contact in CPSF.

101 -encoded proteins responsible for inhibiting CPSF and triggering DoTT(13,15)-did not induce host cell

102 In turn, CstF77 competitively inhibits CPSF-dependent PAP recruitment and 3' polyadenylation.

103 Smicl (Smad-interacting CPSF 30-like) is an unusual protein that interacts with

104 In vitro assays suggest that the 30 kDa CPSF and PABII proteins bind to non-overlapping regions

105 beta-CASP (named for metallo-beta-lactamase, CPSF, Artemis, Snm1, Pso2) domain.

106 Second, the 100-kDa subunit of X. laevis CPSF forms a specific complex with RNAs that contain bot

107 epletion of the 100-kDa subunit of X. laevis CPSF reduces CPE-specific polyadenylation in vitro.

108 orm of the 100-kDa subunit of Xenopus laevis CPSF has now been isolated.

109 three distinct sequence elements by CFI(m), CPSF, and CstF suggests that vertebrate poly(A) site def

110 that observed with highly purified mammalian CPSF and recombinant PAP.

111 in a way that is analogous to the mammalian CPSF complex or their yeast counterparts, and also inter

112 logy with the 73 kD subunit of the mammalian CPSF complex.

113 Surprisingly, CPEB, Maskin, CPSF, and several other factors involved in polyadenylat

114 specifically recognized by the multisubunit CPSF (cleavage and polyadenylation specificity factor) c

115 e homologue of the 30-kDa subunit of nuclear CPSF is also localized to the cytoplasm of X. laevis ooc

116 teraction with the 30-kDa subunit of nuclear CPSF, prevents cytoplasmic polyadenylation, suggesting t

117 at the amino acid sequence level to nuclear CPSF isolated from Bos taurus thymus.

118 egraded by the 5'-3' exonuclease activity of CPSF-73, which also depends on Lsm11.

119 mRNA abundance, and decreased association of CPSF and CstF subunits with the INTS6 locus.

120 P was required for the stable association of CPSF complex to pre-mRNA and then CPSF 73 specifically c

121 nhance both 3' processing and the binding of CPSF in the context of the heterologous core poly(A) sit

122 appears to rely primarily on the binding of CPSF to an A(A/U)UAAA hexamer upstream of the cleavage s

123 27 or IAV NS1 or pharmacological blockade of CPSF activity induced accumulation of host cell Z-RNAs a

124 U1A protein is not an integral component of CPSF but may be able to interact and affect its activity

125 cleavage and termination: core components of CPSF and CstF complex stimulate both cleavage and termin

126 Further support for a cytoplasmic form of CPSF comes from evidence that a putative homologue of th

127 ndicate that a distinct, cytoplasmic form of CPSF is an integral component of the cytoplasmic polyade

128 ding factors, CPEB and a cytoplasmic form of CPSF, control polyadenylation.

129 these results shed light on the function of CPSF in mediating PAS-dependent RNA cleavage and polyade

130 sion that CF II is the functional homolog of CPSF.

131 pact of U3 sequences upon the interaction of CPSF at the core poly(A) site may therefore represent a

132 cessing enhancer promotes the interaction of CPSF with the AAUAAA hexamer.

133 ecombinant U1A stabilized the interaction of CPSF with the AAUAAA-containing substrate RNA in electro

134 role in activating the endonuclease mode of CPSF-73 but is dispensable for its 5'-3' exonuclease act

135 ta-lactamase superfamily and is a paralog of CPSF-73, the endonuclease for pre-mRNA 3'-end processing

136 The active site of CPSF-73, with two zinc ions, is located at the interface

137 U3 sequences also enhanced the stability of CPSF binding at the core poly(A) site.

138 analyses of fractions from various stages of CPSF purification indicated that U1A copurified with CPS

139 . laevis homologue of the 100-kDa subunit of CPSF in the cytoplasmic polyadenylation reaction.

140 smic X. laevis form of the 30-kDa subunit of CPSF is involved in this reaction.

141 ZF4-ZF5 recruits the hFip1 subunit of CPSF, although the details of this interaction have not

142 nteracts with the cellular 30 kDa subunit of CPSF, an essential component of the 3' end processing ma

143 g, and occurs through the 160 kDa subunit of CPSF.

144 striking similarity to the 73-kDa subunit of CPSF.

145 eracts with the WDR33 and CPSF73 subunits of CPSF.

146 RNA 3'-ends in a manner analagous to that of CPSF in the mammalian system.

147 e similarities of CF II subunits to those of CPSF supports the hypothesis that CF II functions in the

148 nized specifically by zinc finger 2 (ZF2) of CPSF-30 and the A4 and A5 bases by ZF3.

149 cleavage and polyadenylation factor (CPF or CPSF).

150 ition, cross-linking studies have pinpointed CPSF-73 as the endonuclease, which catalyzes the cleavag

151 ore the in vivo structural features of plant CPSF, we used tandem affinity purification methods to is

152 These results show that plant CPSF possesses distinct features, such as AtCPSF73-II an

153 Interestingly, these two unique plant CPSF components have been associated with embryo develop

154 two-hybrid data, we propose an in vivo plant CPSF model in which the Arabidopsis CPSF possesses AtCPS

155 ecifies which mRNAs undergo polyadenylation; CPSF, a multifactor complex that interacts with the near

156 ns as an essential scaffold and preorganizes CPSF-30 and WDR33 for high-affinity binding to AAUAAA.

157 tein to the 30 kDa protein in vitro prevents CPSF binding to the RNA substrate and inhibits 3' end cl

158 the substrate, and the related yeast protein CPSF-100 (Ydh1) at 2.5 A resolution.

159 lytic core, but did not require the putative CPSF interaction domain of PAP.

160 Purified recombinant CPSF-73 possesses RNA endonuclease activity, and mutatio

161 ion of Eg2-phosphorylated CPEB is to recruit CPSF into an active cytoplasmic polyadenylation complex.

162 This required the seven-subunit CPSF as well as three additional protein factors: cleava

163 Sustained CPSF expression in undifferentiated keratinocytes requir

164 JTE-607, which targets CPSF-73, is the first known CPA inhibitor (CPAi) in mamm

165 We demonstrate that CPSF contains two copies of hFip1, each binding to the z

166 the first direct experimental evidence that CPSF-73 is the pre-mRNA 3'-end-processing endonuclease.

167 d in vivo assays, we unexpectedly found that CPSF subunits CPSF30 and Wdr33 directly contact AAUAAA.

168 We discuss the hypothesis that CPSF is required for all polyadenylation reactions, but

169 Genome-wide analysis reveals that CPSF also mediates alternative splicing of many internal

170 Accordingly, we show that CPSF/SYMPK is also a cofactor of NOVA2 and heterologous

171 These studies suggest that CPSF-73 is both the endonuclease and 5'-3' exonuclease i

172 These results suggest that CPSF-73, the catalytic component in both reactions, can

173 on the Xrn2 5' exonuclease, suggesting that CPSF-73 degrades the DCP both in vitro and in vivo.

174 These findings imply that CPSFs intrinsic RNA sequence preferences are sufficient

175 The CPSF subunit CPSF160 has been implicated in AAUAAA recog

176 ind specifically to an RS-like region in the CPSF subunit Fip1, and this interaction is inhibited by

177 Yth1, the yeast homolog of the CPSF 30-kDa subunit, is not detected in this complex.

178 e, clipper ( clp ), encodes a homolog of the CPSF 30K subunit.

179 CPSF100, a key subunit of the CPSF complex for polyadenylation regulation, is SUMOylat

180 omotes DOG1 expression by recruitment of the CPSF complex to enhance the proximal cleavage and polyad

181 llectively, we propose that targeting of the CPSF complex, leading to widespread alternative polyaden

182 tion in vitro through the recruitment of the CPSF subunit hFip1 and poly(A) polymerase to the RNA sub

183 protein complexes for each component of the CPSF subunits using Arabidopsis (Arabidopsis thaliana ec

184 here Star-PAP binds to the RNA, recruits the CPSF complex to the 3'-end of pre-mRNA and then defines

185 or two) exhibits significant homology to the CPSF 100-kDa subunit.

186 ciation of CPSF complex to pre-mRNA and then CPSF 73 specifically cleaved the mRNA at the 3'-cleavage

187 These CPSF homologues interact with each other in a way that i

188 R inhibition also induces co-transcriptional CPSF recruitment to gene promoters, predisposing the sel

189 quaternary complex of human CPSF-160, WDR33, CPSF-30, and an AAUAAA RNA at 3.4-A resolution.

190 ain PR8, expressing an NS1 variant with weak CPSF binding, does not induce host shutoff but only APA.

191 am of the cleavage site that dictate whether CPSF-73 functions as an endonuclease or a 5' exonuclease

192 ruited to the transcription unit, along with CPSF and CstF, during the initial stages of transcriptio

193 he NS1 protein is physically associated with CPSF 30 kDa.

194 Overall, our data are consistent with CPSF endonuclease activation and site-specific pre-mRNA

195 ification indicated that U1A copurified with CPSF to a point but could be separated in the highly pur

196 subunit of CPF, RBBP6 does not copurify with CPSF and is recruited in an RNA-dependent manner.

197 truncated version specifically interact with CPSF-73, strongly suggesting that in vitro, the same pro

198 to the cleavage complex by interacting with CPSF 160.

199 een, we identify that HNRNPA3 interacts with CPSF and enhances GRHL3 IpA.

200 s with CstF-77, which in turn interacts with CPSF.

201 RBFOX2 interacts with CPSF/SYMPK and recruits it to the pre-mRNA.