IndraLab
Statements
reach
"Moreover, interactions between eIF4G and the poly [A] binding protein Pab1 are capable of mediating interactions between the 5 ' and 3 ' ends of mRNA [XREF_BIBR], whereby Pab1 stimulates both translation initiation [XREF_BIBR, XREF_BIBR] and deadenylation by the Pan2 and Pan3 complex [XREF_BIBR]."
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"The Pan3 homodimer binds a single Pan2 chain, and the crystal structure of ctPan3 bound to the interacting linker region of ctPan2 (residues 355-406) shows an extensive interface between the two subunits consistent with the integral role of Pan3 in the overall function of the complex."
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"Progressive deadenylation (by the Ccr4-Not or Pan2 and Pan3 complexes in yeast or PARN and PAN2 and PAN3 in metazoans) leads to loss of associated poly (A)-binding protein (PABP) [XREF_BIBR, XREF_BIBR] and subsequently to complete exonucleolytic digestion that proceeds either 5 ' to 3 ', and is decapping dependent, or 3 ' to 5 ', and is decapping independent [XREF_BIBR, XREF_BIBR]."
sparser
"Although Ccr4-Not has roles in many aspects of regulating gene expression (e.g., chromatin remodeling, transcription, mRNA export, and RNA interference), its most defined and best understood role is in mRNA degradation, serving as the major cytoplasmic deadenylase other than Pan2-Pan3 ( xref , xref )."
sparser
"The exonuclease active site of Pan2 additionally selects for poly(A) RNA because it recognizes an intrinsic, single-stranded helical conformation of RNA that is uniquely formed by poly(A) ( xref ) xref Pan2-Pan3 can be recruited to specific transcripts via an interaction with the GW182 protein within the miRNA-induced silencing complex (miRISC) xref , xref , but it remains unclear how or if Pan2-Pan3 is specifically recruited to other transcripts."
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"As the deadenylation process generally occurs in a biphasic manner in mammals, in which long poly (A) tails are first gradually shortened by the PAN2 and PAN3 complex to ~ 100nt, followed by the CCR4, CAF1, and NOT complex to 8-12nt XREF_BIBR, it is possible that multiple deadenylases act on the same mRNA with discrete but overlapping functions."
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"These include the conserved, trimeric Pan2 and Pan3 complex, composed of a single Pan2 catalytic subunit bound to a Pan3 dimer, the PARN deadenylase, which is absent in single cellular eukaryotes, and less-well characterized enzymes, such as the circadian deadenylase Nocturnin, and the Caf1z and Ccr4d complex."
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"Second, direct biochemical interactions link miRNAs to Argonaute, Argonaute to TNRC6, and TNRC6 to the deadenylase complexes (the PAN2 and PAN3 complex and the CCR4 and NOT complex) that shorten the poly (A) tail, thereby showing how the mRNA degradation machinery can be actively recruited independent of either the act or the consequence of translational repression."
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"It may be that the S. pombe Pan2 and Pan3 complex has a role in nuclear trimming of poly (A) tails, as has been shown in budding yeast XREF_BIBR, XREF_BIBR, rather than a role in mRNA decay, as is the case in higher eukaryotes XREF_BIBR, XREF_BIBR, though this would not explain the observed increase in mRNA uridylation in pan2increment and pan3increment cells (XREF_FIG)."
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"Even though the PAN2 and PAN3 complex binds to the GW182 complex XREF_BIBR, XREF_BIBR and the overexpression of a catalytically inactive PAN2 mutant slows down deadenylation XREF_BIBR, the PAN2 and PAN3 complex is not essential for miRNA mediated deadenylation XREF_BIBR, XREF_BIBR."
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"Eukaryotic mRNA deadenylation is generally considered as a two-step process in which the PAN2 and PAN3 complex initiates the poly (A) tail degradation while, in the second step, the CCR4 and NOT complex completes deadenylation, leading to decapping and degradation of the mRNA body."
sparser
"The Pan3 homodimer binds a single Pan2 chain, and the crystal structure of ct Pan3 bound to the interacting linker region of ct Pan2 (residues 355–406) shows an extensive interface between the two subunits consistent with the integral role of Pan3 in the overall function of the complex."
sparser
"Biochemical and structural studies of yeast factors indicate that Pan2-Pan3 can efficiently trim long PATs with serially bound PABP in part because of a unique architecture of PABP-PABP interactions on poly(A), whereas Pan2-Pan3 is inefficient on short poly(A)-PABP mRNPs ( xref )."
sparser
"Although Ccr4-Not activity removes the final part of the poly(A) tail, and is often thought of as being ‘faster’ than Pan2-Pan3, it is clear that it does not act equally on all short poly(A) tails because stable, highly-translated transcripts are more resistant to deadenylation."
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"One study has described a series of coupled events starting with the recruitment of the translation termination factors eRF1 and eRF3, recruitment of the minor deadenylation complex Pan2 and Pan3, and finally recruitment of Ccr4-Not by the BTG and TOB family of proteins via their interaction with PABP.88 BTG and TOB proteins are absent in budding and fission yeast and they are not constitutively expressed in mammalian cells (for reviews see Ref 89)."
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"Such differences would be expected if miRNAs preferentially direct the deadenylation of shorter tails, as might be inferred from reports that (1) miRNA function depends more on recruitment of the CCR4-NOT deadenylase complex than it does on recruitment of the PAN2-PAN3 deadenylase complex, and (2) the CCR4-NOT deadenylase complex acts at a later, more processive step of mRNA deadenylation than does the PAN2 and PAN3 complex."
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"The novel t (7; 13) (p14; q12)/PAN3-PSMA2 in the neoplastic bone marrow cells could affect two key protein complex : (a) the PAN2 and PAN3 complex (PAN3 rearrangement) which is responsible for deadenylation, the process of removing the poly (A) tail from RNA, and (b) the proteasome (PSMA2 rearrangement) which is responsible for degradation of intracellular proteins."
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"Of the other parasitic protists examined to date for deadenylation machinery, Trypanosoma brucei has been shown to contain both the Ccr4 -Not complex and the Pan2 and Pan3 complex [XREF_BIBR, XREF_BIBR], while Plasmodium falciparum contained a majority of the required components of the Ccr4 and Not complex but was also missing the Pan2 and Pan3 complex [XREF_BIBR]."
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"Considering that (i) NOT1 interacts with NOT2 [reviewed in], (b) the PAN2 and PAN3 complex interacts with PABP and (c) the CCR4-NOT and PAN2-PAN3 complexes form a larger multiprotein complex in vivo, our observations indicate a high degree of connectivity and redundancy within the GW182 interaction network, which could explain why mutations in individual motifs do not abolish partner binding or silencing activity, but a combination of two or more mutations is required to abrogate binding and silencing activity."