ライフサイエンスコーパス: CPSF

1 CPSF-160 functions as an essential scaffold and preorgan

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

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

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

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

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

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

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

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

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

11 t stimulates an interaction between CPEB and CPSF.

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

13 ex with the polyadenylation factors CstF and CPSF.

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

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

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

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

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

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

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

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

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

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

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

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

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

27 litates recognition of the AAUAAA hexamer by CPSF.

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

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

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

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

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

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

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

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

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

37 cleavage site and recruits the endonuclease CPSF-73.

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

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

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

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

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

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

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

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

46 vage and polyadenylation specificity factor (CPSF) complex.

47 vage and polyadenylation specificity factor (CPSF) complex.

48 vage and polyadenylation specificity factor (CPSF) complex.

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

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

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

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

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

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

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

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

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

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

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

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

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

62 vage and polyadenylation specificity factor (CPSF).

63 cleavage/polyadenylation specificity factor (CPSF).

64 cleavage-polyadenylation specificity factor (CPSF).

65 vage and polyadenylation specificity factor (CPSF).

66 vage and polyadenylation specificity factor (CPSF).

67 vage and polyadenylation specificity factor (CPSF).

68 vage and polyadenylation specificity factor (CPSF).

69 vage and Polyadenylation Specificity Factor (CPSF).

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

138 The CPSF subunit CPSF160 has been implicated in AAUAAA recog

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

154 to the cleavage complex by interacting with CPSF 160.

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

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