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Karla M Neugebauer - One of the best experts on this subject based on the ideXlab platform.
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Good Cap/bad Cap: how the Cap-Binding Complex determines RNA fate
Nature Structural & Molecular Biology, 2014Co-Authors: Michaela Müller-mcnicoll, Karla M NeugebauerAbstract:Every RNA polymerase II transcript receives a 5′-end 7-methylguanosine (m^7G) Cap, which is rapidly bound by the nuclear Cap–Binding Complex (CBC). Two recent studies now reveal that the CBC associates with a variety of effector proteins that enable it to interrogate nascent RNA, discriminating between distinct RNA subclasses and routing them either toward distinct maturation pathways or toward decay. Thus, the CBC has an early role in policing cellular RNA.
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good Cap bad Cap how the Cap Binding Complex determines rna fate
Nature Structural & Molecular Biology, 2014Co-Authors: Michaela Mullermcnicoll, Karla M NeugebauerAbstract:Every RNA polymerase II transcript receives a 5′-end 7-methylguanosine (m7G) Cap, which is rapidly bound by the nuclear Cap–Binding Complex (CBC). Two recent studies now reveal that the CBC associates with a variety of effector proteins that enable it to interrogate nascent RNA, discriminating between distinct RNA subclasses and routing them either toward distinct maturation pathways or toward decay. Thus, the CBC has an early role in policing cellular RNA.
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the nuclear Cap Binding Complex interacts with the u4 u6 u5 tri snrnp and promotes spliceosome assembly in mammalian cells
RNA, 2013Co-Authors: Marta Pabis, Noa Neufeld, Michaela C Steiner, Teodora Bojic, Yaron Shavtal, Karla M NeugebauerAbstract:The nuclear Cap-Binding Complex (CBC) binds to the 7-methyl guanosine Cap present on every RNA polymerase II transcript. CBC has been implicated in many aspects of RNA biogenesis; in addition to roles in miRNA biogenesis, nonsense-mediated decay, 3′-end formation, and snRNA export from the nucleus, CBC promotes pre-mRNA splicing. An unresolved question is how CBC participates in splicing. To investigate CBC’s role in splicing, we used mass spectrometry to identify proteins that copurify with mammalian CBC. Numerous components of spliceosomal snRNPs were specifically detected. Among these, three U4/U6·U5 snRNP proteins (hBrr2, hPrp4, and hPrp31) copurified with CBC in an RNA-independent fashion, suggesting that a significant fraction of CBC forms a Complex with the U4/U6·U5 snRNP and that the activity of CBC might be associated with snRNP recruitment to pre-mRNA. To test this possibility, CBC was depleted from HeLa cells by RNAi. Chromatin immunoprecipitation and live-cell imaging assays revealed decreased cotranscriptional accumulation of U4/U6·U5 snRNPs on active transcription units, consistent with a requirement for CBC in cotranscriptional spliceosome assembly. Surprisingly, recruitment of U1 and U2 snRNPs was also affected, indicating that RNA-mediated interactions between CBC and snRNPs contribute to splicing. On the other hand, CBC depletion did not impair snRNP biogenesis, ruling out the possibility that decreased snRNP recruitment was due to changes in nuclear snRNP concentration. Taken together, the data support a model whereby CBC promotes pre-mRNA splicing through a network of interactions with and among spliceosomal snRNPs during cotranscriptional spliceosome assembly.
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The nuclear Cap-Binding Complex interacts with the U4/U6·U5 tri-snRNP and promotes spliceosome assembly in mammalian cells
RNA (New York N.Y.), 2013Co-Authors: Marta Pabis, Noa Neufeld, Michaela C Steiner, Teodora Bojic, Yaron Shav-tal, Karla M NeugebauerAbstract:The nuclear Cap-Binding Complex (CBC) binds to the 7-methyl guanosine Cap present on every RNA polymerase II transcript. CBC has been implicated in many aspects of RNA biogenesis; in addition to roles in miRNA biogenesis, nonsense-mediated decay, 3′-end formation, and snRNA export from the nucleus, CBC promotes pre-mRNA splicing. An unresolved question is how CBC participates in splicing. To investigate CBC’s role in splicing, we used mass spectrometry to identify proteins that copurify with mammalian CBC. Numerous components of spliceosomal snRNPs were specifically detected. Among these, three U4/U6·U5 snRNP proteins (hBrr2, hPrp4, and hPrp31) copurified with CBC in an RNA-independent fashion, suggesting that a significant fraction of CBC forms a Complex with the U4/U6·U5 snRNP and that the activity of CBC might be associated with snRNP recruitment to pre-mRNA. To test this possibility, CBC was depleted from HeLa cells by RNAi. Chromatin immunoprecipitation and live-cell imaging assays revealed decreased cotranscriptional accumulation of U4/U6·U5 snRNPs on active transcription units, consistent with a requirement for CBC in cotranscriptional spliceosome assembly. Surprisingly, recruitment of U1 and U2 snRNPs was also affected, indicating that RNA-mediated interactions between CBC and snRNPs contribute to splicing. On the other hand, CBC depletion did not impair snRNP biogenesis, ruling out the possibility that decreased snRNP recruitment was due to changes in nuclear snRNP concentration. Taken together, the data support a model whereby CBC promotes pre-mRNA splicing through a network of interactions with and among spliceosomal snRNPs during cotranscriptional spliceosome assembly.
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Binding properties and dynamic localization of an alternative isoform of the Cap-Binding Complex subunit CBP20
Nucleus (Austin Tex.), 2010Co-Authors: Marta Pabis, Noa Neufeld, Yaron Shav-tal, Karla M NeugebauerAbstract:The nuclear Cap-Binding Complex (CBC) is a heterodimer composed of CBP20 and CBP80 subunits and has roles in the biogenesis of messenger RNAs (mRNAs), small nuclear RNAs (snRNAs) and microRNAs. CBP20 is a phylogenetically conserved protein that interacts with the 7-methyl guanosine (m7G) Cap added to the 5' end of all RNA polymerase II transcripts. CBP80 ensures high affinity Binding of the Cap by CBP20 and provides a platform for interactions with other factors. Here we characterize an alternative splice variant of CBP20, termed CBP20S. The CBP20S transcript has an in-frame deletion, leading to the translation of a protein lacking most of the RNA recognition motif (RRM). We show that CBP20S is conserved among mammalian species and is expressed in human cell lines and bone marrow cells. Unlike the full-length CBP20, CBP20S does not bind CBP80 or the m7G Cap. Nevertheless, CBP20S does bind mRNA, is localized to an active transcription site, and redistributed to nucleolar Caps upon transcription inhibition....
Iain W. Mattaj - One of the best experts on this subject based on the ideXlab platform.
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Co-crystallization of the human nuclear Cap-Binding Complex with a m7GpppG Cap analogue using protein engineering.
Acta crystallographica. Section D Biological crystallography, 2002Co-Authors: Catherine Mazza, Alexandra Segref, Iain W. Mattaj, Stephen CusackAbstract:The nuclear Cap-Binding Complex (CBC) binds the 7-methyl-G(5')ppp(5')N Cap structure at the 5' end of pre-messenger and uracil-rich small nuclear RNAs in the nucleus. It mediates interaction of these Capped RNAs with various nuclear machineries involved in RNA maturation and is co-exported with them to the cytoplasm. The structure of human CBC, which comprises the subunits CBP20 and CBP80, has previously been determined in a mildly trypsinated form which can no longer bind the Cap. Here, the engineering and crystallization of two variant CBCs with deletions in CBP80 which do not affect function are described. A Complex with a small N-terminal deletion in CBP80 was crystallized in space group C2 with one Complex per asymmetric unit. The crystals diffract to 2 A resolution and give the first structure of intact but Cap-free CBC. An additional internal deletion in CBP80 of a prominent solvent-exposed coiled coil gives rise to a more compact Complex. This was co-crystallized with the Cap analogue m(7)GpppG in two different crystal forms which could grow in the same drop. Form 1 belongs to space group P3(1)21 with one Complex per asymmetric unit and diffracts to 2.15 A resolution. Form 2 belongs to space group P2(1)2(1)2(1) with two Complexes per asymmetric unit and diffracts to 2.3 A resolution. In both forms, strong extra electron density is observed for the Cap analogue and for the N- and C-terminal extensions of CBP20 which was absent or disordered in all previous structures.
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Large-scale induced fit recognition of an m7GpppG Cap analogue by the human nuclear Cap-Binding Complex
The EMBO journal, 2002Co-Authors: Catherine Mazza, Alexandra Segref, Iain W. Mattaj, Stephen CusackAbstract:The heterodimeric nuclear Cap-Binding Complex (CBC) binds to the 5′ Cap structure of RNAs in the nucleus and plays a central role in their diverse maturation steps. We describe the crystal structure at 2.1 Å resolution of human CBC bound to an m7GpppG Cap analogue. Comparison with the structure of unComplexed CBC shows that Cap Binding induces co-operative folding around the dinucleotide of some 50 residues from the N- and C-terminal extensions to the central RNP domain of the small subunit CBP20. The Cap-bound conformation of CBP20 is stabilized by an intricate network of interactions both to the ligand and within the subunit, as well as new interactions of the CBP20 N-terminal tail with the large subunit CBP80. Although the structure is very different from that of other known Cap-Binding proteins, such as the cytoplasmic Cap-Binding protein eIF4E, specificity for the methylated guanosine again is achieved by sandwiching the base between two aromatic residues, in this case two conserved tyrosines. Implications for the transfer of Capped mRNAs to eIF4E, required for translation initiation, are discussed.
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Crystal Structure of the Human Nuclear Cap Binding Complex
Molecular cell, 2001Co-Authors: Catherine Mazza, Mutsuhito Ohno, Alexandra Segref, Iain W. Mattaj, Stephen CusackAbstract:Abstract The heterodimeric nuclear Cap Binding Complex (CBC) binds to 5′-Capped polymerase II transcripts. It enhances the efficiency of several mRNA maturation steps and is essential for U snRNA nuclear export in multicellular eukaryotes. The 2A crystal structure of human CBC shows that the large subunit, CBP80, comprises three domains, each containing consecutive helical hairpins and resembling the so-called MIF4G domain found in several other proteins involved in RNA metabolism. The small subunit, CPB20, has an RNP fold and associates with the second and third domains of CBP80. Site-directed mutagenesis revealed 4 residues of CBP20 which are critical for Cap Binding. A model for Cap Binding is proposed based on these results and the known mode of Binding of RNA to RNP domains.
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The yeast nuclear Cap Binding Complex can interact with translation factor eIF4G and mediate translation initiation.
Molecular cell, 2000Co-Authors: Puri Fortes, Toshifumi Inada, Thomas Preiss, Matthias W. Hentze, Iain W. Mattaj, Alan B. SachsAbstract:The mRNA Cap structure is bound by either the nuclear (CBC) or the cytoplasmic (eIF4F) Cap Binding Complex. Following mRNA export, CBC must be exchanged for eIF4F in the cytoplasm. It is not known how this exchange occurs or how this RNP remodeling event is integrated with mRNA function. Here we report genetic and biochemical evidence that the yeast translation initiation factor eIF4G associates with CBC, and that eIF4E, the eIF4F component that binds both the Cap and eIF4G, antagonizes this interaction. Furthermore, we find that CBC can stimulate translation in extracts containing an eIF4G protein deficient for eIF4E Binding. These data suggest that eIF4E Binding to the eIF4G-CBC Complex on newly exported mRNA displaces CBC, and that the first round of translation on mRNA may occur via a different mechanism than subsequent rounds.
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Genetic and physical interactions involving the yeast nuclear Cap-Binding Complex.
Molecular and cellular biology, 1999Co-Authors: Puri Fortes, Joanna Kufel, Maarten Fornerod, Maria Polycarpou-schwarz, Denis L.j. Lafontaine, David Tollervey, Iain W. MattajAbstract:Yeast strains lacking the yeast nuclear Cap-Binding Complex (yCBC) are viable, although impaired in growth. We have taken advantage of this observation to carry out a genetic screen for components that show synthetic lethality (SL) with a cbp20-D cbp80-D double mutation. One set of SL interactions was due to mutations that were complemented by components of U1 small nuclear RNP (snRNP) and the yeast splicing commitment Complex. These interactions confirm the role of yCBC in commitment Complex formation. Physical interaction of yCBC with the commitment Complex components Mud10p and Mud2p, which may directly mediate yCBC function, was demonstrated. Unexpectedly, we identified multiple SL mutations that were complemented by Cbf5p and Nop58p. These are components of the two major classes of yeast small nucleolar RNPs, which function in the maturation of rRNA precursors. Mutants lacking yCBC were found to be defective in rRNA processing. Analysis of the yCBC deletion phenotype suggests that this is likely to be due to a defect in the splicing of a subset of ribosomal protein mRNA precursors. Most eukaryotic organisms have a complement of three specialized RNA polymerases (pol I, pol II, and pol III) responsible mainly for rRNA, mRNA, and tRNA synthesis, respectively. pol II transcripts have characteristic 59 ends consisting of a 7-methylguanosine Cap structure attached by a 59-59 phosphotriester linkage to the first encoded nucleotide of the transcript (66). Aside from providing protection against 59-to-39 exonuclease activities, the Cap structure plays important roles at multiple steps in the function of pol II transcripts. In vertebrates, the Cap has been shown to stimulate pre-mRNA splicing (30, 37, 38, 57), pre-mRNA 39 end formation by cleavage and polyadenylation (11, 15, 19, 23), export from the nucleus of U small nuclear RNAs (snRNAs) (22, 32), and the initiation of translation (67).
Stephen Cusack - One of the best experts on this subject based on the ideXlab platform.
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Structural analysis of human ARS2 as a platform for co-transcriptional RNA sorting.
Nature communications, 2018Co-Authors: Wiebke Manuela Schulze, Frank Stein, Mandy Rettel, Max H. Nanao, Stephen CusackAbstract:ARS2 is a highly conserved metazoan protein involved in numerous aspects of nuclear RNA metabolism. As a direct partner of the nuclear Cap-Binding Complex (CBC), it mediates interactions with diverse RNA processing and transport machineries in a transcript-dependent manner. Here, we present the human ARS2 crystal structure, which exhibits similarities and metazoan-specific differences to the plant homologue SERRATE, most notably an additional RRM domain. We present biochemical, biophysical and cellular interactome data comparing wild type and mutant ARS2 that identify regions critical for interactions with FLASH (involved in histone mRNA biogenesis), NCBP3 (a putative Cap-Binding protein involved in mRNA export) and single-stranded RNA. We show that FLASH and NCBP3 have overlapping Binding sites on ARS2 and that CBC–ARS2–NCBP3 form a ternary Complex that is mutually exclusive with CBC–ARS–PHAX (involved in snRNA export). Our results support that mutually exclusive higher-order CBC–ARS2 Complexes are critical in determining Pol II transcript fate. Arsenic resistance protein 2 (ARS2) plays an important role in nuclear RNA metabolism and interacts with the nuclear Cap-Binding Complex (CBC). Here the authors present the human ARS2 structure and identify regions important for its interactions with Binding partners supporting that mutually exclusive higher order CBC-ARS2 Complexes are formed.
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cbc ars2 stimulates 3 end maturation of multiple rna families and favors Cap proximal processing
Nature Structural & Molecular Biology, 2013Co-Authors: Marie Hallais, Frédéric Pontvianne, Peter Refsing Andersen, Marcello Clerici, Daniela Lener, Nour El Houda Benbahouche, Thierry Gostan, Franck Vandermoere, Marie-cécile Robert, Stephen CusackAbstract:The nuclear Cap–Binding Complex (CBC) stimulates RNA maturation, but the mechanistic basis is not well understood. In vitro reconstitution experiments combined with functional analyses have revealed a new CBC Complex containing ARS2, a major effector of CBC. ARS2 links the Cap to 3'-end maturation for several RNA families, thus favoring the production of short RNAs.
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CBC–ARS2 stimulates 3′-end maturation of multiple RNA families and favors Cap-proximal processing
Nature Structural & Molecular Biology, 2013Co-Authors: Marie Hallais, Frédéric Pontvianne, Peter Refsing Andersen, Marcello Clerici, Daniela Lener, Nour El Houda Benbahouche, Thierry Gostan, Franck Vandermoere, Marie-cécile Robert, Stephen CusackAbstract:The nuclear Cap–Binding Complex (CBC) stimulates RNA maturation, but the mechanistic basis is not well understood. In vitro reconstitution experiments combined with functional analyses have revealed a new CBC Complex containing ARS2, a major effector of CBC. ARS2 links the Cap to 3'-end maturation for several RNA families, thus favoring the production of short RNAs.
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diverse role of three tyrosines in Binding of the rna 5 Cap to the human nuclear Cap Binding Complex
Journal of Molecular Biology, 2009Co-Authors: Remigiusz Worch, Catherine Mazza, Stephen Cusack, Anna Niedzwiecka, Janusz Stepinski, Edward Darzynkiewicz, Marzena Jankowskaanyszka, Ryszard StolarskiAbstract:The heterodimeric nuclear Cap-Binding Complex (CBC) specifically recognizes the monomethylguanosine 5′ Cap structure of the eukaryotic RNA polymerase II transcripts such as mRNA and U snRNA. The Binding is essential for nuclear maturation of mRNA, for nuclear export of U snRNA in metazoans, and for nonsense-mediated decay of mRNA and the pioneer round of translation. We analysed the recognition of the Cap by native human CBC and mutants in which each tyrosine that stacks with the 7-methylguanosine moiety was replaced by phenylalanine or alanine and both tyrosines were replaced by phenylalanines. The equilibrium association constants (Kas) for two selected Cap analogues, P1-7-methylguanosine-5′ P3-guanosine-5′ triphosphate and 7-methylguanosine triphosphate, were determined by two independent methods, fluorescence titration and surface plasmon resonance. We could distinguish two tyrosines, Y43 and Y20, in stabilization of the Cap inside the CBC-Binding pocket. In particular, lack of Y20 in CBC leads to a greater affinity of the mono- than the dinucleotide Cap analogue, in contrast to the wild-type protein. A crucial role of cation–π stacking in the mechanism of the specific Cap recognition by CBC was postulated from the comparison of the experimentally derived Gibbs free Binding energy (ΔG°) with the stacking energy (ΔE) of the 7-methylguanosine/Y binary and ternary Complexes calculated by the Moller–Plesset second-order perturbation method. The resulting kinetic model of the association between the Capped RNA and CBC, based on the experimental data and quantum calculations, is discussed with respect to the “CBC-to-eukaryotic initiation factor 4E handoff” of mRNA.
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Diverse Role of Three Tyrosines in Binding of the RNA 5′ Cap to the Human Nuclear Cap Binding Complex
Journal of molecular biology, 2008Co-Authors: Remigiusz Worch, Catherine Mazza, Stephen Cusack, Anna Niedzwiecka, Janusz Stepinski, Marzena Jankowska-anyszka, Edward Darzynkiewicz, Ryszard StolarskiAbstract:The heterodimeric nuclear Cap-Binding Complex (CBC) specifically recognizes the monomethylguanosine 5′ Cap structure of the eukaryotic RNA polymerase II transcripts such as mRNA and U snRNA. The Binding is essential for nuclear maturation of mRNA, for nuclear export of U snRNA in metazoans, and for nonsense-mediated decay of mRNA and the pioneer round of translation. We analysed the recognition of the Cap by native human CBC and mutants in which each tyrosine that stacks with the 7-methylguanosine moiety was replaced by phenylalanine or alanine and both tyrosines were replaced by phenylalanines. The equilibrium association constants (Kas) for two selected Cap analogues, P1-7-methylguanosine-5′ P3-guanosine-5′ triphosphate and 7-methylguanosine triphosphate, were determined by two independent methods, fluorescence titration and surface plasmon resonance. We could distinguish two tyrosines, Y43 and Y20, in stabilization of the Cap inside the CBC-Binding pocket. In particular, lack of Y20 in CBC leads to a greater affinity of the mono- than the dinucleotide Cap analogue, in contrast to the wild-type protein. A crucial role of cation–π stacking in the mechanism of the specific Cap recognition by CBC was postulated from the comparison of the experimentally derived Gibbs free Binding energy (ΔG°) with the stacking energy (ΔE) of the 7-methylguanosine/Y binary and ternary Complexes calculated by the Moller–Plesset second-order perturbation method. The resulting kinetic model of the association between the Capped RNA and CBC, based on the experimental data and quantum calculations, is discussed with respect to the “CBC-to-eukaryotic initiation factor 4E handoff” of mRNA.
Kang Yan - One of the best experts on this subject based on the ideXlab platform.
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Dual roles of the Serine/Arginine-rich splicing factor SR45a in promoting and interacting with nuclear Cap-Binding Complex to modulate the salt stress response in Arabidopsis.
The New phytologist, 2021Co-Authors: Qianhuan Guo, Peng Liu, Jinguang Huang, Shizhong Zhang, Guodong Yang, Chengchao Zheng, Kang YanAbstract:Alternative splicing (AS) is emerging as a critical co-transcriptional regulation for plants in response to environmental stresses. Although multiple splicing factors have been linked to the salt-sensitive signaling network, the molecular mechanism remains unclear. We discovered that a conserved SR-like protein, SR45a, as a component of the spliceosome, was involved in post-transcriptional regulation of salinity tolerance in Arabidopsis thaliana. Furthermore, SR45a was required for the AS and mRNA maturation of several salt-tolerance genes. Two alternatively spliced variants of SR45a were induced by salt stress, full-length SR45a-1a and the truncated isoform SR45a-1b, respectively. Lines with overexpression of SR45a-1a and SR45a-1b exhibited hypersensitive to salt stress. Our data indicated that SR45a directly interacted with the Cap-Binding Complex (CBC) subunit Cap-Binding protein 20 (CBP20) which mediated salt stress responses. Instead of Binding to other spliceosome components, SR45a-1b promoted the association of SR45a-1a with CBP20, therefore mediating salt stress signal transduction pathways. Additionally, the mutations in SR45a and CBP20 led to different salt stress phenotypes. Together, these results provide the evidence that SR45a-CBP20 acts as a regulatory Complex to regulate the plant response to salt stress, through a regulatory mechanism to fine-tune the splicing factors, especially in stressful conditions.
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dual roles of the serine arginine rich splicing factor sr45a in promoting and interacting with nuclear Cap Binding Complex to modulate the salt stress response in arabidopsis
New Phytologist, 2021Co-Authors: Qianhuan Guo, Peng Liu, Jinguang Huang, Shizhong Zhang, Guodong Yang, Chengchao Zheng, Kang YanAbstract:Alternative splicing (AS) is emerging as a critical co-transcriptional regulation for plants in response to environmental stresses. Although multiple splicing factors have been linked to the salt-sensitive signaling network, the molecular mechanism remains unclear. We discovered that a conserved SR-like protein, SR45a, as a component of the spliceosome, was involved in post-transcriptional regulation of salinity tolerance in Arabidopsis thaliana. Furthermore, SR45a was required for the AS and mRNA maturation of several salt-tolerance genes. Two alternatively spliced variants of SR45a were induced by salt stress, full-length SR45a-1a and the truncated isoform SR45a-1b, respectively. Lines with overexpression of SR45a-1a and SR45a-1b exhibited hypersensitive to salt stress. Our data indicated that SR45a directly interacted with the Cap-Binding Complex (CBC) subunit Cap-Binding protein 20 (CBP20) which mediated salt stress responses. Instead of Binding to other spliceosome components, SR45a-1b promoted the association of SR45a-1a with CBP20, therefore mediating salt stress signal transduction pathways. Additionally, the mutations in SR45a and CBP20 led to different salt stress phenotypes. Together, these results provide the evidence that SR45a-CBP20 acts as a regulatory Complex to regulate the plant response to salt stress, through a regulatory mechanism to fine-tune the splicing factors, especially in stressful conditions.
Dapeng Zhang - One of the best experts on this subject based on the ideXlab platform.
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arabidopsis translation initiation factors eifiso4g1 2 link repression of mrna Cap Binding Complex eifiso4f assembly with rna Binding protein soar1 mediated aba signaling
New Phytologist, 2019Co-Authors: Shangchuan Jiang, Chao Mei, Xiaofang Wang, Dapeng ZhangAbstract:The translation initiation factor eIF4E-Binding protein-mediated regulation of protein translation by interfering with assembly of mRNA Cap-Binding Complex eIF4F is well described in mammalian and yeast cells. However, it remains unknown whether a signaling regulator or pathway interacts directly with any translation initiation factor to modulate assembly of eIF4F in plant cells. Here, we report that the two isoforms of Arabidopsis eIF4G, eIFiso4G1 and eIFiso4G2, interact with a cytoplasmic-nuclear dual-localized pentatricopeptide repeat protein SOAR1 to regulate abscisic acid (ABA) signaling. SOAR1 inhibits interactions of eIFiso4E, eIF4Es, eIF4A1, eIF4B2 and poly(A)-Binding protein PAB6 with eIFiso4G1 and eIFiso4G2, thereby inhibiting eIFiso4F/mixed eIF4F assembly and repressing translation initiation. SOAR1 binds mRNA of a key ABA-responsive gene ABI5 and cooperates with eIFiso4G1/2 to repress translation of ABI5. The Binding of SOAR1 to ABI5 mRNA is likely to inhibit the interaction of SOAR1 with eIFiso4G1/2, suggesting a regulatory loop. Our findings identify a novel translation initiation repressor interfering with Cap-Binding Complex assembly, and establish a link between Cap-Binding Complex assembly and ABA signaling.
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Arabidopsis translation initiation factors eIFiso4G1/2 link repression of mRNA Cap-Binding Complex eIFiso4F assembly with RNA-Binding protein SOAR1-mediated ABA signaling.
The New phytologist, 2019Co-Authors: Shangchuan Jiang, Chao Mei, Xiaofang Wang, Dapeng ZhangAbstract:The translation initiation factor eIF4E-Binding protein-mediated regulation of protein translation by interfering with assembly of mRNA Cap-Binding Complex eIF4F is well described in mammalian and yeast cells. However, it remains unknown whether a signaling regulator or pathway interacts directly with any translation initiation factor to modulate assembly of eIF4F in plant cells. Here, we report that the two isoforms of Arabidopsis eIF4G, eIFiso4G1 and eIFiso4G2, interact with a cytoplasmic-nuclear dual-localized pentatricopeptide repeat protein SOAR1 to regulate abscisic acid (ABA) signaling. SOAR1 inhibits interactions of eIFiso4E, eIF4Es, eIF4A1, eIF4B2 and poly(A)-Binding protein PAB6 with eIFiso4G1 and eIFiso4G2, thereby inhibiting eIFiso4F/mixed eIF4F assembly and repressing translation initiation. SOAR1 binds mRNA of a key ABA-responsive gene ABI5 and cooperates with eIFiso4G1/2 to repress translation of ABI5. The Binding of SOAR1 to ABI5 mRNA is likely to inhibit the interaction of SOAR1 with eIFiso4G1/2, suggesting a regulatory loop. Our findings identify a novel translation initiation repressor interfering with Cap-Binding Complex assembly, and establish a link between Cap-Binding Complex assembly and ABA signaling.