Pabp2: Biological Overview | References
Gene name - Pabp2
Cytological map position-44B3-44B3
Function - RNA-binding protein
Keywords - nuclear polyadenylation of mRNAs, cytoplasmic regulation of poly(A) tail length
Symbol - Pabp2
FlyBase ID: FBgn0005648
Genetic map position - 2R: 4,018,918..4,021,879 [+]
Classification - RRM, RNA recognition motif protein
Cellular location - nuclear and cytoplasmic
Translational control of maternal mRNA through regulation of poly(A) tail length is crucial during early development. The nuclear poly(A) binding protein, PABP2, was identified biochemically from its role in nuclear polyadenylation. This study analyzed the in vivo function of PABP2 in Drosophila. PABP2 is required in vivo for polyadenylation, and Pabp2 function, including poly(A) polymerase stimulation, is essential for viability. An unanticipated cytoplasmic function is demonstrated for PABP2 during early development. In contrast to its role in nuclear polyadenylation, cytoplasmic PABP2 acts to shorten the poly(A) tails of specific mRNAs. PABP2, together with the deadenylase CCR4, regulates the poly(A) tails of oskar and cyclin B mRNAs, both of which are also controlled by cytoplasmic polyadenylation. Both Cyclin B protein levels and embryonic development depend upon this regulation. These results identify a regulator of maternal mRNA poly(A) tail length and highlight the importance of this mode of translational control (Benoit, 2005).
During early development in most species, regulation of gene expression is strictly posttranscriptional. One major posttranscriptional regulatory mechanism involves variations in poly(A) tail length, which regulate mRNA expression by affecting both mRNA stability and translation. Cytoplasmic changes in mRNA poly(A) tail length by deadenylation and polyadenylation play, thus, an essential role in controlling the production of key proteins during early development. While cytoplasmic polyadenylation has been studied extensively, the mechanisms underlying the control of poly(A) tail length in the cytoplasm are unknown (Benoit, 2005).
In Xenopus oocytes, cytoplasmic poly(A) tail elongation requires cis elements, including the cytoplasmic polyadenylation element (CPE) located in the 3' UTR of mRNAs and the nuclear polyadenylation signal, AAUAAA. CPEs are bound by the CPE binding protein (CPEB; see Drosophila CPEB, Orb), a primary factor in cytoplasmic polyadenylation, which also requires a poly(A) polymerase (PAP) and a complex that binds the AAUAAA element, called the Cleavage and Polyadenylation Specificity Factor (CPSF) (Mendez, 2000). Cytoplasmic elongation of the poly(A) tail leads to translational activation by remodeling the mRNP: in the repressed state, a translational repressor called Maskin binds to CPEB and eIF4E, the cap binding initiation factor, and precludes the eIF4E-eIF4G interaction that is required for translation initiation. When polyadenylation occurs, the elongated poly(A) tail is bound by the cytoplasmic poly(A) binding protein, PABP, which then interacts with eIF4G. This promotes the association between eIF4E and eIF4G (Cao, 2002), thereby allowing translation initiation (Benoit, 2005).
The role of the poly(A) tail in translational control in Drosophila is more controversial. In early embryos, a long poly(A) tail is both necessary and sufficient to induce translation of bicoid and Toll mRNAs, which encode the anterior morphogen and a determinant of dorsoventral polarity, respectively (Salles, 1994; Schisa, 1998). Translation of the posterior determinant oskar (osk) mRNA, is also highly regulated during oogenesis. Translation is repressed until mid-oogenesis, and subsequently in the oocyte, as osk mRNA is being transported to the posterior pole. During this transport, a major translational repressor is Bruno, whose mechanism of action was found to be independent of the 5' cap and the poly(A) tail in vitro. A recent study, however, has identified a new translational repressor of osk mRNA, called Cup, which interacts with both Bruno and eIF4E. This strongly suggests that Cup/Bruno-mediated translational repression is cap-dependent, acting to prevent the eIF4E-eIF4G interaction in a manner similar to Maskin. While the mechanism underlying the release of Bruno repression at the posterior pole is unknown, accumulation of Osk protein at the posterior of the oocyte requires osk mRNA cytoplasmic polyadenylation involving Orb, the Drosophila homolog of CPEB and Drosophila PAP (Benoit, 2005 and references therein).
Before cytoplasmic regulation can occur, poly(A) tails are added to mRNAs in the nucleus in a cotranscriptional reaction involving endonucleolytic cleavage followed by polyadenylation (Wahle, 1999). In mammals, the reaction involves two signals flanking the cleavage site, the upstream polyadenylation signal, AAUAAA, and a downstream GU-rich element. Cleavage requires several cleavage factors, including CPSF, and polyadenylation of cleaved RNAs can be recapitulated in vitro with CPSF, PAP, and the nuclear poly(A) binding protein, PABP2 (PABPN1 in mammals) (Bienroth, 1993). While PAP has a very low affinity for, and binds aspecifically to, RNA, specificity is achieved through the recognition of the AAUAAA element by CPSF, which then tethers PAP to the RNA by direct protein-protein interaction. While CPSF thus stimulates PAP, complete stimulation occurs only in the additional presence of PABP2, which binds the poly(A) tail when it has reached ten residues in size. At this point, the reaction becomes processive, and a complete poly(A) tail is synthesized very rapidly and without dissociation of PAP from the RNA. PABP2 has a second function in nuclear polyadenylation, namely, to control poly(A) tail length: once the poly(A) tail has reached full length (250 residues in mammalian cells), the reaction becomes slow and distributive (Wahle, 1995). These two functions of PABP2 in nuclear polyadenylation are carried out by different domains of the protein, and they can be uncoupled by point mutations (Kerwitz, 2003). These data have led to a model in which multiple PABP2 proteins coat the growing poly(A) tail, with only one of them directly interacting with PAP (Benoit, 2005).
Although PABP2 is nuclear at steady-state levels in somatic cells, it shuttles from nuclear to cytoplasmic compartments (Calado, 2000). While a possible role for PABP2 in mRNA export has not been investigated, PABP2 has been found to be associated with an mRNA during its docking at the nuclear pore, and it was present on the cytoplasmic side of the nuclear envelope (Bear, 2003). This suggests that the exchange between nuclear PABP2 and cytoplasmic PABP on poly(A) tails occurs in the cytoplasm (Benoit, 2005).
This study used Pabp2 mutants to address the in vivo role of PABP2 in Drosophila.PABP2 has a role in poly(A) tail lengthening in somatic tissues, and that this function is essential for viability. The cytoplasmic presence of PABP2 is described in oocytes and early embryos (Benoit, 1999; full text of article), and it is shown that cytoplasmic PABP2 binds to poly(A) tails at these stages and shortens poly(A) tails of specific mRNAs, in conjunction with the deadenylase CCR4. Cytoplasmic poly(A) tail length control by PABP2 is essential for development, as embryos depleted of PABP2 show early developmental arrest, with elongated poly(A) tails of key maternal mRNAs (Benoit, 2005).
An important set of biochemical data has led to a precise description of PABP2 function in nuclear polyadenylation (Kühn, 2004). In in vitro polyadenylation assays, PABP2 has two distinct roles: it stimulates PAP to make polyadenylation processive, and it controls poly(A) tail length, with polyadenylation becoming distributive once the tail has reached 250 nucleotides. This length control involves a measurement of the poly(A) tail by PABP2 (Wahle, 1995). Drosophila PABP2 tested in mammalian polyadenylation-reconstituted assays also shows these two functions (Benoit, 1999). Using a null Pabp2 allele, this study shows that poly(A) tails measured either on total or on individual mRNAs are shorter in Pabp2 mutants than they are in wild-type, consistent with a role for PABP2 in poly(A) tail elongation. The short poly(A) tails in mutant embryos appear to result from deadenylation of existing mRNAs and progressive reduction of new mRNA synthesis as the PABP2 level decreases. Poly(A) tails of newly synthesized Hsp70 mRNA were of similar size in the Pabp255 mutant and in wild-type, although they were present in a small amount in the mutant and were thought to be synthesized with the remaining maternal PABP2. The finding that newly synthesized mRNAs with short poly(A) tails do not accumulate when PABP2 is limiting suggests that PABP2 is absolutely required for polyadenylation and that PAP is unable to produce stable poly(A) tails in the absence of PABP2. In agreement with this, it was found that PABP2 is essential for viability, and specifically for cell viability, since Pabp255 mutant somatic or germline clones were found to not survive. Moreover, lethality in the absence of PAPB2 may be caused by a lack of PAP stimulation, since a Pabp2 transgene bearing a point mutation that prevents PAP stimulation is unable to rescue the lethality of the null allele Pabp255. Taken together, these results strongly suggest that the function of PABP2 in mRNA polyadenylation is essential, and that PAP in the absence of PABP2 is incapable of producing stable polyadenylated mRNAs (Benoit, 2005).
One important conclusion presented in this paper is the identification of an unexpected function for PABP2 in regulating poly(A) tail length of cytoplasmic mRNAs during early development. Using two hypomorphic Pabp2 alleles, it was found that a reduced amount of PABP2 leads to elongated poly(A) tails in two mRNAs regulated by cytoplasmic polyadenylation. Three sets of data indicate that this function of PABP2 is cytoplasmic: (1) the poly(A) tail elongation phenotype on the involved mRNAs is the opposite of the Pabp2 mutant phenotype on total mRNAs, also visible in the same RNA preparations on the control sop mRNA; (2) a reduced level of PABP2 restores longer poly(A) tails on osk and cyc B mRNAs, but not on sop mRNA, in orbmel ovaries in which cytoplasmic polyadenylation is impaired; (3) PABP2 is cytoplasmic in oocytes, and in early embryos prior to the onset of zygotic transcription, it binds poly(A) tails of mRNAs that are also bound by the cytoplasmic proteins Orb and PABP, and it is recruited into cytoplasmic cyc B mRNA particles (Benoit, 2005).
This cytoplasmic function of PABP2 is essential for early development. PABP2 is required to shorten poly(A) tails of, at least, osk and cyc B mRNAs, and in Pabp2 mutant germline clones the lengthening of cyc B poly(A) tails correlates with higher levels of Cyc B protein and with embryonic phenotypes similar to those produced by a high dosage of maternal Cyc B. Misregulation of other maternal mRNAs could also contribute to the lethality of embryos from these germline clones, since cytoplasmic PABP2 probably regulates several of them. The maternal-effect embryonic lethality of Pabp26 is strongly rescued by the Pabp2-I61S transgene, which lacks the nuclear function of PAP stimulation; this suggests that this lethality results from a defect in the cytoplasmic function of PABP2. In addition, the synergistic effect of the simultaneous decrease in PABP2 and CCR4 amounts in the female germline, which leads to important embryonic lethality and elongated poly(A) tails of osk and cyc B mRNAs, also indicates an essential function of cytoplasmic PABP2 in shortening poly(A) tails at these stages. Finally, consistent with PABP2 playing a major role in the cytoplasm during early development is the recent identification (Good, 2004) of a cytoplasmic PABP2 specific to embryos in Xenopus and mouse (Benoit, 2005).
Several lines of evidence suggest that PABP2 regulates poly(A) tail length in the cytoplasm by using a different mechanism than that used during nuclear polyadenylation. Termination of poly(A) tail elongation during nuclear polyadenylation is thought to result from a PABP2-dependent remodeling of the polyadenylation complex that blocks PAP stimulation. This remodeling depends on the complete coating of the poly(A) tail by PABP2 (Kerwitz, 2003). In sharp contrast, studies of cytoplasmic polyadenylation in Drosophila embryos suggest that the reaction is not processive and does not involve PAP stimulation by PABP2. Cytoplasmic polyadenylation of bicoid mRNA in embryos is slow, with poly(A) tail elongation depending on the level of PAP (Juge, 2002). Very long poly(A) tails are produced by overexpression of PAP, without poly(A) tail length control. Consistent with this, it was found that cytoplasmic PABP and PABP2 are present on the same mRNA poly(A) tails in ovary and early embryo extracts, thereby precluding complete coating of the poly(A) tail by PABP2 (Benoit, 2005).
In yeast, poly(A) tail length control involves deadenylation by the PAN (Pan2/Pan3) deadenylase, which is activated by poly(A) tail bound PABP (Brown, 1998). It is proposed that, similarly, during early Drosophila development, cytoplasmic PABP2 controls the poly(A) tail length of key mRNAs whose turnover and translatability are specifically regulated, by modulating the activity of a deadenylase. Poly(A) tail length control of these mRNAs would thus be achieved by the balance between cytoplasmic polyadenylation and deadenylation. A major deadenylation complex in Drosophila is the CCR4/NOT complex, in which CCR4 is the deadenylase (Temme, 2004). ccr4 function is essential in the female germline, where it regulates poly(A) tail lengths of cyc B mRNA and other cell cycle regulators (Morris, 2005). This study found that Pabp2 and ccr4 act in conjunction in shortening poly(A) tails of specific mRNAs, consistent with a possible role of PABP2 in stimulation of CCR4 activity. In yeast, deadenylation by the CCR4/NOT complex is inhibited in vitro by PABP (Tucker, 2002). If this regulation is conserved in metazoans, the presence of PABP2 on poly(A) tails could modulate this effect of PABP (Benoit, 2005).
The 3' poly(A) tail of eukaryotic mRNAs and the poly(A) binding protein (PABP) play important roles in the regulation of translation. Recently, a human PABP-interacting protein, Paip2, which disrupts the PABP-poly(A) interaction and consequently inhibits translation, was described. To gain insight into the biological role of Paip2, the Drosophila Paip2 (dPaip2) was studied. dPaip2 is the bona fide human Paip2 homologue; it interacts with dPABP, inhibits binding of dPABP to the mRNA poly(A) tail, and reduces translation of a reporter mRNA by 80% in an S2 cell-free translation extract. Ectopic overexpression of dPaip2 in Drosophila wings and wing discs results in a size reduction phenotype, which is due to a decrease in cell number. Clones of cells overexpressing dPaip2 in wing discs also contain fewer cells than controls. This phenotype can be explained by a primary effect on cell growth. Indeed, overexpression of dPaip2 in postreplicative tissues inhibits growth, inasmuch as it reduces ommatidia size in eyes and cell size in the larval fat body. It is concluded that dPaip2 inhibits cell growth primarily by inhibiting protein synthesis (Roy, 2004; full text of article).
Two human proteins that interact directly with PABP have been identified: Paip1 and Paip2 (PABP-interacting proteins 1 and -2). Paip1 stimulates, while Paip2 represses, translation (Craig, 1998; Khaleghpour, 2001a). Paip2 inhibits translation by reducing the binding of PABP to the poly(A) tail and by competing with Paip1 for binding to PABP. Paip1 and Paip2 share two conserved PABP-interacting motifs (PAMs). PAM1 consists of a stretch of acidic amino acids in the middle of Paip2 (aa 22 to 75) and at the C terminus of Paip1 (aa 440 to 479), and it binds strongly to RRMs 2 and 3 and to RRMs 1 and 2 of PABP, respectively (Khaleghpour, 2001b; Roy, 2002). The second binding site, PAM2, also called the PABP C-terminal binding motif, resides in the C terminus of Paip2 (aa 106 to 120) (Khaleghpour, 2001a) and the N terminus of Paip1 (aa 123 to 137) (Roy, 2002). PAM2 consists of a short stretch of 15 aa and binds to the C terminus of PABP (within aa 546 to 619) with a lower affinity (10- and 200-fold for Paip1 and Paip2, respectively) than that of the PAM1-PABP interaction. PAM2 is also found in several additional proteins, including eukaryotic release factor 3 (eRF3), ataxin 2, and transducer of ErbB-2 (Tob). Thus, Paip2 and Paip1 might compete with some of these PAM2 binding partners to regulate PABP function. The Drosophila homologue of the human Paip2 (dPaip2), was isolated and characterized. Its ability to interact with Drosophila PABP (dPABP), inhibit translation, and interfere with dPABP poly(A) binding activity was demonstrated. Importantly, dPaip2 inhibits growth in flies (Roy, 2004).
dPaip2 reduces growth without altering patterning in several Drosophila tissues, including the larval fat body, eyes, wings, and wing-imaginal discs. dPaip2 strongly inhibits translation in vitro, as was shown for hPaip2. Thus, dPaip2 most likely inhibits growth by repressing translation. Translation is a major target of growth control, as cells need to increase their protein content before they can divide in order to ensure daughter cell survival. Deregulation of translation has often been associated with growth defects. For example, in Drosophila, a collection of mutations in genes encoding ribosomal proteins (known as Minute mutations) have low overall growth rates and are delayed in development. Interference with the formation of the eIF4F complex at the 5' end of the mRNA by the translation suppressor d4E-BP results in a reduced-growth phenotype. Mutations in the translation initiator factors deIF4E and deIF4A caused a more dramatic larval growth arrest phenotype, which is similar to that seen upon amino acid starvation. It is well established that nutrient starvation causes inhibition of translation by affecting discrete translational-control pathways (Roy, 2004 and references therein).
A number of signaling pathways have been implicated in the promotion of cell growth. Nutrient availability plays a key role in growth, and the insulin-signaling pathway coordinates cellular metabolism with nutritional conditions. The insulin-signaling pathway promotes translation via stimulation of S6K and inactivation of the translational repressor 4E-BP. Ectopic overexpression in Drosophila of positive components of the insulin-signaling pathway, for example, dInr or dPI3K, or mutations in negative regulators, such as dPTEN and dTSC1/2, cause dramatic increases in cell size and, to a lesser extent, increases in cell numbers (reviewed in references. Moreover, mutations in these same positive signaling components, or ectopic overexpression of the negative regulators, such as a highly active version of d4E-BP, primarily reduce cell size and have significantly weaker effects on cell numbers (with the exception of dS6K, which affects only cell size). In addition, increased insulin signaling stimulates transition through the G1/S phases of the cell cycle, but the overall doubling time of these cells is unchanged due to a compensatory lengthening of the G2/M phases. Hence, this pathway seems primarily to stimulate mass accumulation, creating an imbalance between growth and proliferation signals, which results in an alteration of cell size. The reasons for this imbalance remain unclear. dMyc and dRas also control cell growth. Ectopic overexpression of dMyc or activated dRas (dRasV12) promotes growth and results in increased cell size and numbers. Conversely, loss of the dMyc gene inhibits growth and results in fewer and smaller cells. Interestingly, dRas appears to upregulate dMyc at a posttranscriptional level. Similar to the insulin-signaling pathway, overexpression of dMyc and dRas affects growth in an unbalanced fashion, as they also shorten the G1 phase of the cell cycle and the G2 phase is lengthened to compensate. However, these proteins have weaker effects on cell size than components of the insulin-signaling pathway (Roy, 2004 and references therein).
In contrast to the insulin-signaling pathway and to dMyc and dRas, cooverexpression of dCdk4 and dCyclin D promotes growth and accelerates cell cycling. This results in a balanced, proportional cell growth in which cell size remains unchanged while cell numbers increase. Consistent with this finding, deletion of the Cdk4 gene represses growth without altering cell size and leads to a decrease in cell numbers. Interestingly, the phenotypes observed upon loss of the Cdk4 gene are similar to the phenotype of dPaip2 overexpression. In dividing cells of the wing discs, dPaip2 decreases cell numbers without reducing cell size, while in nonproliferating cells of the larval fat body and of the eye, dPaip2 overexpression decreases cell size. These tissue-specific effects are consistent with an inhibition of growth. In proliferating cells, the reduced translation capacity of the dPaip2-overexpressing cells likely affects all phases of the cell cycle equally. The reduced growth of these cells results in longer cell doubling times, but growth remains coordinated with proliferation and cell size is not affected. Consistent with a primary effect on growth, the nonproliferating cells of the eye and the larval fat body are reduced in size owing to impairment in translation. It is unclear at present why d4E-BP overexpression creates an imbalance between growth and proliferation signals, which leads to an alteration in cell size, while dPaip2 does not. The different sensitivities of some mRNAs to these translational inhibitors might be responsible for the different phenotypes (Roy, 2004 and references therein).
What is the molecular mechanism by which dPaip2 mediates its effect on cell growth? A likely possibility is that dPaip2 reduces growth by inhibiting the interaction of dPABP with the poly(A) tail, thus disrupting the mRNA 5'-3' loop and inhibiting translation . eIF4F disproportionately stimulates the translation of mRNAs containing extensive secondary structures in their 5' UTRs, which mainly encode growth factors and their receptors, cyclins, and other mitogens. For example, the level of cyclin D1 increases when eIF4E is overexpressed. Inasmuch as PABP stimulates the translation of a subset of mRNAs by activating eIF4F, dPaip2 inhibition of translation might disproportionately affect the same subset of mRNAs. Cyclin D and Cdk4 are interesting candidates. It would be important to link dPaip2 and cyclin D/Cdk4 translation. In addition, the translation of some mRNAs might be especially sensitive to the level of dPABP or dPaip2 (Roy, 2004).
The phenotypes observed upon overexpression of dPaip2 in different tissues are less dramatic than would have been expected from the in vitro translation experiments (~0% inhibition of translation). It is conceivable that dPaip2 levels in vivo are tightly regulated to prevent deleterious interference with PABP function (PABP's gene is essential). There is one Drosophila homologue of Paip1 (dPaip1) that has not been studied yet. Since Paip1 stimulates translation, it is possible that it counteracts the effects of overexpression of the repressor dPaip2. dPaip2, like Paip1, eRF3, ataxin-2, and Tob, interacts with the C-terminal domain of PABP through its conserved PAM2 site. The different PAM2-containing proteins might compete with Paip2 to modulate the activity of PABP and consequently attenuate the effects of dPaip2 overexpression. Furthermore, since hPaip2 is a phosphoprotein, it is possible that dPaip2 is also a phosphoprotein and that its activity is controlled by its phosphorylation state (Roy, 2004).
In conclusion, dPaip2 is an inhibitor of cell growth, most likely because of its ability to repress translation. This study also highlights the importance of regulating PABP function in translation and growth. This system should serve as a basis to identify regulators of dPaip2 activity by screening for genetic interacting partners (Roy, 2004).
Search PubMed for articles about Drosophila Pabp2
Bear, D.G., et al. (2003). Nuclear poly(A)-binding protein PABPN1 is associated with RNA polymerase II during transcription and accompanies the released transcript to the nuclear pore. Exp. Cell Res. 286: 332-344. PubMed ID: 12749861
Benoit, B., et al. (1999). The Drosophila poly(A)-binding protein II is ubiquitous throughout Drosophila development and has the same function in mRNA polyadenylation as its bovine homolog in vitro. Nucleic Acids Res. 27(19): 3771-8. PubMed ID: 10481015
Benoit, B., et al. (2005). An essential cytoplasmic function for the nuclear poly(A) binding protein, PABP2, in poly(A) tail length control and early development in Drosophila. Dev. Cell. 9(4): 511-22. PubMed ID: 16198293
Bienroth, S., Keller, W. and Wahle, E. (1993). Assembly of a processive mRNA polyadenylation complex. EMBO J. 12: 585-594. PubMed ID: 8440247
Brown, C. E. and Sachs, A. B. (1998). Poly(A) tail length control in Saccharomyces cerevisiae occurs by message-specific deadenylation. Mol. Cell. Biol. 18: 6548-6559. PubMed ID: 9774670
Calado, A., et al. (2000). Deciphering the cellular pathway for transport of poly(A)-binding protein II. RNA 6: 245-256. PubMed ID: 10688363
Cao, Q. and Richter, J. D. (2002). Dissolution of the maskin-eIF4E complex by cytoplasmic polyadenylation and poly(A)-binding protein controls cyclin B1 mRNA translation and oocyte maturation. EMBO J. 21: 3852-3862. PubMed ID: 12110596
Craig, A. W., Haghighat, A., Yu, A. T. and Sonenberg, N. (1998). Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation. Nature 392(6675): 520-3. PubMed ID: 9548260
Good, P.J., Abler, L., Herring, D. and Sheets, M. D. (2004). Xenopus embryonic poly(A) binding protein 2 (ePABP2) defines a new family of cytoplasmic poly(A) binding proteins expressed during the early stages of vertebrate development. Genesis 38: 166-175. PubMed ID: 15083517
Juge, F., Zaessinger, S., Temme, C., Wahle, E. and Simonelig, M. (2002). Control of poly(A) polymerase level is essential to cytoplasmic polyadenylation and early development in Drosophila. EMBO J. 21: 6603-6613. PubMed ID: 12456666
Kerwitz, Y., et al. (2003). Stimulation of poly(A) polymerase through a direct interaction with the nuclear poly(A) binding protein allosterically regulated by RNA, EMBO J. 22: 3705-3714. PubMed ID: 12853485
Khaleghpour, K., et al. (2001a). Translational repression by a novel partner of human poly(A) binding protein. Paip2. Mol. Cell 7: 205-216. PubMed ID: 11172725
Khaleghpour, K., et al. (2001b). Dual interactions of the translational repressor Paip2 with poly(A) binding protein. Mol. Cell. Biol. 21: 5200-5213. PubMed ID: 11438674
Kühn, U. and Wahle, E. (2004). Structure and function of poly(A) binding proteins. Biochim. Biophys. Acta 1678: 67-84. PubMed ID: 15157733
Mendez, R., et al. (2000). Phosphorylation of CPEB by Eg2 mediates the recruitment of CPSF into an active cytoplasmic polyadenylation complex, Mol. Cell 6: 1253-1259. PubMed ID: 11106762
Morris, Z., Hong, A., Lilly, M. A. and Lehmann, R. (2005). twin, a CCR4 homolog, regulates cyclin poly(A) tail length to permit Drosophila oogenesis. Development 132: 1165-1174. PubMed ID: 15703281
Roy, G., et al. (2002). Paip1 interacts with poly(A) binding protein through two independent binding motifs. Mol. Cell. Biol. 22: 3769-3782. PubMed ID: 11997512
Roy, G., Miron, M., Khaleghpour, K., Lasko, P. and Sonenberg, N. (2004). The Drosophila poly(A) binding protein-interacting protein, dPaip2, is a novel effector of cell growth. Mol. Cell. Biol. 24(3): 1143-54. PubMed ID: 14729960
Salles, F. J. et al. (1994). Coordinate initiation of Drosophila development by regulated polyadenylation of maternal messenger RNAs. Science 266: 1996-1999. PubMed ID: 7801127
Schisa, J. A. and Strickland, S. (1998). Cytoplasmic polyadenylation of Toll mRNA is required for dorsal-ventral patterning in Drosophila embryogenesis. Development 125: 2995-3003. PubMed ID: 9655821
Temme, C., et al. (2004). A complex containing the CCR4 and CAF1 proteins is involved in mRNA deadenylation in Drosophila. EMBO J. 23. 2862-2871. PubMed ID: 15215893
Tucker, M., et al. (2002). Ccr4p is the catalytic subunit of a Ccr4p/Pop2p/Notp mRNA deadenylase complex in Saccharomyces cerevisiae, EMBO J. 21: 1427-1436. PubMed ID: 11889048
Wahle, E. and Rüegsegger, U. (1999). 3'-end processing of pre-mRNA in eukaryotes, FEMS Microbiol. Rev. 23: 277-295. PubMed ID: 10371034
date revised: 15 February 2008
Home page: The Interactive Fly © 2008 Thomas Brody, Ph.D.
The Interactive Fly resides on the
Society for Developmental Biology's Web server.