The Experts below are selected from a list of 240 Experts worldwide ranked by ideXlab platform
Barbara K. Felber - One of the best experts on this subject based on the ideXlab platform.
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The RNA Transport Element of the Murine musD Retrotransposon Requires Long-range Intramolecular Interactions for Function
The Journal of biological chemistry, 2010Co-Authors: Michal Legiewicz, Andrei S. Zolotukhin, Guy R. Pilkington, Katarzyna J. Purzycka, Michelle Mitchell, Hiroaki Uranishi, Jenifer Bear, George N. Pavlakis, Stuart F. J. Le Grice, Barbara K. FelberAbstract:Abstract Retrovirus replication requires specialized Transport mechanisms to export genomic mRNA from the nucleus to the cytoplasm of the infected cell. This regulation is mediated by a combination of viral and/or cellular factors that interact with cis-acting RNA export elements linking the viral RNA to the cellular CRM1 or NXF1 nuclear export pathways. Endogenous type D murine LTR retrotransposons (musD) were reported to contain an RNA export element located upstream of the 3′-LTR. Although functionally equivalent, the musD export element, termed the musD Transport element, is distinct from the other retroviral RNA export elements, such as the constitutive Transport element of simian/Mason-Pfizer monkey retroviruses and the RNA Transport element found in rodent intracisteRNAl A-particle LTR retrotransposons. We demonstrate here that the minimal RNA Transport element (musD Transport element) of musD comprises multiple secondary structure elements that presumably serve as recognition signals for the cellular export machinery. We identified two classes of tertiary interactions, namely kissing loops and a pseudoknot. This work constitutes the first example of an RNA Transport element requiring such structural motifs to mediate nuclear export.
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The RNA Transport element RTE is essential for IAP LTR-retrotransposon mobility.
Virology, 2008Co-Authors: Andrei S. Zolotukhin, Hiroaki Uranishi, Jenifer Bear, George N. Pavlakis, Sergey Smulevitch, Daniel Michalowski, Ralf Schneider, Irina Tretyakova, Sean O'keeffe, Barbara K. FelberAbstract:We previously identified an RNA Transport element (RTE) present at a high copy number in the mouse genome. Here, we show that a related element, RTE-D, is part of a mobile LTR-retrotransposon, which belongs to a family of intracisteRNAl A-particle related elements (IAP). We demonstrate that RTE-D is essential for the mobility of the retrotransposon and it can be substituted by other known RNA export signals. RTE-deficient IAP transcripts are retained in the nucleus, while the RTE-containing transcripts accumulate in the cytoplasm allowing Gag protein expression. RTE-D acts as a posttranscriptional control element in a heterologous reporter mRNA and is activated by the cellular RNA binding protein 15 (RBM15), as reported for the previously described RTE. We identified a complex family of RTE-containing IAPs in mouse and mapped the active RTE-D-containing IAPs to the Mmr10 group of LTR-retrotransposons. These data reveal that, despite a complex evolutionary history, retroelements and retroviruses share the dependency on posttranscriptional regulation.
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RNA-binding motif protein 15 binds to the RNA Transport element RTE and provides a direct link to the NXF1 export pathway.
The Journal of biological chemistry, 2006Co-Authors: Susan Lindtner, Andrei S. Zolotukhin, Hiroaki Uranishi, Jenifer Bear, Barbara K. Felber, Sergey Smulevitch, Viraj Kulkarni, Martina Samiotaki, George Panayotou, George N. PavlakisAbstract:Retroviruses/retroelements provide tools enabling the identification and dissection of basic steps for post-transcriptional regulation of cellular mRNAs. The RNA Transport element (RTE) identified in mouse retrotransposons is functionally equivalent to constitutive Transport element of Type D retroviruses, yet does not bind directly to the mRNA export receptor NXF1. Here, we report that the RNA-binding motif protein 15 (RBM15) recognizes RTE directly and specifically in vitro and stimulates export and expression of RTE-containing reporter mRNAs in vivo. Tethering of RBM15 to a reporter mRNA showed that RBM15 acts by promoting mRNA export from the nucleus. We also found that RBM15 binds to NXF1 and the two proteins cooperate in stimulating RTE-mediated mRNA export and expression. Thus, RBM15 is a novel mRNA export factor and is part of the NXF1 pathway. We propose that RTE evolved as a high affinity RBM15 ligand to provide a splicing-independent link to NXF1, thereby ensuring efficient nuclear export and expression of retrotransposon transcripts.
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Structural and Functional Analysis of the RNA Transport Element, a Member of an Extensive Family Present in the Mouse Genome
Journal of virology, 2005Co-Authors: Sergey Smulevitch, Andrei S. Zolotukhin, Jenifer Bear, George N. Pavlakis, Daniel Michalowski, Ralf Schneider, Patricia Roth, Barbara K. FelberAbstract:We previously identified an RNA Transport element (RTE), present in a subclass of rodent intracisteRNAl A particle retroelements (F. Nappi, R. Schneider, A. Zolotukhin, S. Smulevitch, D. Michalowski, J. Bear, B. Felber, and G. Pavlakis, J. Virol. 75:4558-4569, 2001), that is able to replace Rev-responsive element regulation in human immunodeficiency virus type 1. RTE-directed mRNA export is mediated by a still-unknown cellular factor(s), is independent of the CRM1 nuclear export receptor, and is conserved among vertebrates. Here we show that this RTE folds into an extended RNA secondary structure and thus does not resemble any known RTEs. Computer searches revealed the presence of 105 identical elements and more than 3,000 related elements which share at least 70% sequence identity with the RTE and which are found on all mouse chromosomes. These related elements are predicted to fold into RTE-like structures. Comparison of the sequences and structures revealed that the RTE and related elements can be divided into four groups. Mutagenesis of the RTE revealed that the minimal element contains four inteRNAl stem-loops, which are indispensable for function in mammalian cells. In contrast, only part of the element is essential to mediate RNA Transport in microinjected Xenopus laevis oocyte nuclei. Importantly, the minimal RTE able to promote RNA Transport has key structural features which are preserved in all the RTE-related elements, further supporting their functional importance. Therefore, RTE function depends on a complex secondary structure that is important for the interaction with the cellular export factor(s).
George N. Pavlakis - One of the best experts on this subject based on the ideXlab platform.
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The RNA Transport Element of the Murine musD Retrotransposon Requires Long-range Intramolecular Interactions for Function
The Journal of biological chemistry, 2010Co-Authors: Michal Legiewicz, Andrei S. Zolotukhin, Guy R. Pilkington, Katarzyna J. Purzycka, Michelle Mitchell, Hiroaki Uranishi, Jenifer Bear, George N. Pavlakis, Stuart F. J. Le Grice, Barbara K. FelberAbstract:Abstract Retrovirus replication requires specialized Transport mechanisms to export genomic mRNA from the nucleus to the cytoplasm of the infected cell. This regulation is mediated by a combination of viral and/or cellular factors that interact with cis-acting RNA export elements linking the viral RNA to the cellular CRM1 or NXF1 nuclear export pathways. Endogenous type D murine LTR retrotransposons (musD) were reported to contain an RNA export element located upstream of the 3′-LTR. Although functionally equivalent, the musD export element, termed the musD Transport element, is distinct from the other retroviral RNA export elements, such as the constitutive Transport element of simian/Mason-Pfizer monkey retroviruses and the RNA Transport element found in rodent intracisteRNAl A-particle LTR retrotransposons. We demonstrate here that the minimal RNA Transport element (musD Transport element) of musD comprises multiple secondary structure elements that presumably serve as recognition signals for the cellular export machinery. We identified two classes of tertiary interactions, namely kissing loops and a pseudoknot. This work constitutes the first example of an RNA Transport element requiring such structural motifs to mediate nuclear export.
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The RNA Transport element RTE is essential for IAP LTR-retrotransposon mobility.
Virology, 2008Co-Authors: Andrei S. Zolotukhin, Hiroaki Uranishi, Jenifer Bear, George N. Pavlakis, Sergey Smulevitch, Daniel Michalowski, Ralf Schneider, Irina Tretyakova, Sean O'keeffe, Barbara K. FelberAbstract:We previously identified an RNA Transport element (RTE) present at a high copy number in the mouse genome. Here, we show that a related element, RTE-D, is part of a mobile LTR-retrotransposon, which belongs to a family of intracisteRNAl A-particle related elements (IAP). We demonstrate that RTE-D is essential for the mobility of the retrotransposon and it can be substituted by other known RNA export signals. RTE-deficient IAP transcripts are retained in the nucleus, while the RTE-containing transcripts accumulate in the cytoplasm allowing Gag protein expression. RTE-D acts as a posttranscriptional control element in a heterologous reporter mRNA and is activated by the cellular RNA binding protein 15 (RBM15), as reported for the previously described RTE. We identified a complex family of RTE-containing IAPs in mouse and mapped the active RTE-D-containing IAPs to the Mmr10 group of LTR-retrotransposons. These data reveal that, despite a complex evolutionary history, retroelements and retroviruses share the dependency on posttranscriptional regulation.
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RNA-binding motif protein 15 binds to the RNA Transport element RTE and provides a direct link to the NXF1 export pathway.
The Journal of biological chemistry, 2006Co-Authors: Susan Lindtner, Andrei S. Zolotukhin, Hiroaki Uranishi, Jenifer Bear, Barbara K. Felber, Sergey Smulevitch, Viraj Kulkarni, Martina Samiotaki, George Panayotou, George N. PavlakisAbstract:Retroviruses/retroelements provide tools enabling the identification and dissection of basic steps for post-transcriptional regulation of cellular mRNAs. The RNA Transport element (RTE) identified in mouse retrotransposons is functionally equivalent to constitutive Transport element of Type D retroviruses, yet does not bind directly to the mRNA export receptor NXF1. Here, we report that the RNA-binding motif protein 15 (RBM15) recognizes RTE directly and specifically in vitro and stimulates export and expression of RTE-containing reporter mRNAs in vivo. Tethering of RBM15 to a reporter mRNA showed that RBM15 acts by promoting mRNA export from the nucleus. We also found that RBM15 binds to NXF1 and the two proteins cooperate in stimulating RTE-mediated mRNA export and expression. Thus, RBM15 is a novel mRNA export factor and is part of the NXF1 pathway. We propose that RTE evolved as a high affinity RBM15 ligand to provide a splicing-independent link to NXF1, thereby ensuring efficient nuclear export and expression of retrotransposon transcripts.
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Structural and Functional Analysis of the RNA Transport Element, a Member of an Extensive Family Present in the Mouse Genome
Journal of virology, 2005Co-Authors: Sergey Smulevitch, Andrei S. Zolotukhin, Jenifer Bear, George N. Pavlakis, Daniel Michalowski, Ralf Schneider, Patricia Roth, Barbara K. FelberAbstract:We previously identified an RNA Transport element (RTE), present in a subclass of rodent intracisteRNAl A particle retroelements (F. Nappi, R. Schneider, A. Zolotukhin, S. Smulevitch, D. Michalowski, J. Bear, B. Felber, and G. Pavlakis, J. Virol. 75:4558-4569, 2001), that is able to replace Rev-responsive element regulation in human immunodeficiency virus type 1. RTE-directed mRNA export is mediated by a still-unknown cellular factor(s), is independent of the CRM1 nuclear export receptor, and is conserved among vertebrates. Here we show that this RTE folds into an extended RNA secondary structure and thus does not resemble any known RTEs. Computer searches revealed the presence of 105 identical elements and more than 3,000 related elements which share at least 70% sequence identity with the RTE and which are found on all mouse chromosomes. These related elements are predicted to fold into RTE-like structures. Comparison of the sequences and structures revealed that the RTE and related elements can be divided into four groups. Mutagenesis of the RTE revealed that the minimal element contains four inteRNAl stem-loops, which are indispensable for function in mammalian cells. In contrast, only part of the element is essential to mediate RNA Transport in microinjected Xenopus laevis oocyte nuclei. Importantly, the minimal RTE able to promote RNA Transport has key structural features which are preserved in all the RTE-related elements, further supporting their functional importance. Therefore, RTE function depends on a complex secondary structure that is important for the interaction with the cellular export factor(s).
Andrei S. Zolotukhin - One of the best experts on this subject based on the ideXlab platform.
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The RNA Transport Element of the Murine musD Retrotransposon Requires Long-range Intramolecular Interactions for Function
The Journal of biological chemistry, 2010Co-Authors: Michal Legiewicz, Andrei S. Zolotukhin, Guy R. Pilkington, Katarzyna J. Purzycka, Michelle Mitchell, Hiroaki Uranishi, Jenifer Bear, George N. Pavlakis, Stuart F. J. Le Grice, Barbara K. FelberAbstract:Abstract Retrovirus replication requires specialized Transport mechanisms to export genomic mRNA from the nucleus to the cytoplasm of the infected cell. This regulation is mediated by a combination of viral and/or cellular factors that interact with cis-acting RNA export elements linking the viral RNA to the cellular CRM1 or NXF1 nuclear export pathways. Endogenous type D murine LTR retrotransposons (musD) were reported to contain an RNA export element located upstream of the 3′-LTR. Although functionally equivalent, the musD export element, termed the musD Transport element, is distinct from the other retroviral RNA export elements, such as the constitutive Transport element of simian/Mason-Pfizer monkey retroviruses and the RNA Transport element found in rodent intracisteRNAl A-particle LTR retrotransposons. We demonstrate here that the minimal RNA Transport element (musD Transport element) of musD comprises multiple secondary structure elements that presumably serve as recognition signals for the cellular export machinery. We identified two classes of tertiary interactions, namely kissing loops and a pseudoknot. This work constitutes the first example of an RNA Transport element requiring such structural motifs to mediate nuclear export.
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The RNA Transport element RTE is essential for IAP LTR-retrotransposon mobility.
Virology, 2008Co-Authors: Andrei S. Zolotukhin, Hiroaki Uranishi, Jenifer Bear, George N. Pavlakis, Sergey Smulevitch, Daniel Michalowski, Ralf Schneider, Irina Tretyakova, Sean O'keeffe, Barbara K. FelberAbstract:We previously identified an RNA Transport element (RTE) present at a high copy number in the mouse genome. Here, we show that a related element, RTE-D, is part of a mobile LTR-retrotransposon, which belongs to a family of intracisteRNAl A-particle related elements (IAP). We demonstrate that RTE-D is essential for the mobility of the retrotransposon and it can be substituted by other known RNA export signals. RTE-deficient IAP transcripts are retained in the nucleus, while the RTE-containing transcripts accumulate in the cytoplasm allowing Gag protein expression. RTE-D acts as a posttranscriptional control element in a heterologous reporter mRNA and is activated by the cellular RNA binding protein 15 (RBM15), as reported for the previously described RTE. We identified a complex family of RTE-containing IAPs in mouse and mapped the active RTE-D-containing IAPs to the Mmr10 group of LTR-retrotransposons. These data reveal that, despite a complex evolutionary history, retroelements and retroviruses share the dependency on posttranscriptional regulation.
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RNA-binding motif protein 15 binds to the RNA Transport element RTE and provides a direct link to the NXF1 export pathway.
The Journal of biological chemistry, 2006Co-Authors: Susan Lindtner, Andrei S. Zolotukhin, Hiroaki Uranishi, Jenifer Bear, Barbara K. Felber, Sergey Smulevitch, Viraj Kulkarni, Martina Samiotaki, George Panayotou, George N. PavlakisAbstract:Retroviruses/retroelements provide tools enabling the identification and dissection of basic steps for post-transcriptional regulation of cellular mRNAs. The RNA Transport element (RTE) identified in mouse retrotransposons is functionally equivalent to constitutive Transport element of Type D retroviruses, yet does not bind directly to the mRNA export receptor NXF1. Here, we report that the RNA-binding motif protein 15 (RBM15) recognizes RTE directly and specifically in vitro and stimulates export and expression of RTE-containing reporter mRNAs in vivo. Tethering of RBM15 to a reporter mRNA showed that RBM15 acts by promoting mRNA export from the nucleus. We also found that RBM15 binds to NXF1 and the two proteins cooperate in stimulating RTE-mediated mRNA export and expression. Thus, RBM15 is a novel mRNA export factor and is part of the NXF1 pathway. We propose that RTE evolved as a high affinity RBM15 ligand to provide a splicing-independent link to NXF1, thereby ensuring efficient nuclear export and expression of retrotransposon transcripts.
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Structural and Functional Analysis of the RNA Transport Element, a Member of an Extensive Family Present in the Mouse Genome
Journal of virology, 2005Co-Authors: Sergey Smulevitch, Andrei S. Zolotukhin, Jenifer Bear, George N. Pavlakis, Daniel Michalowski, Ralf Schneider, Patricia Roth, Barbara K. FelberAbstract:We previously identified an RNA Transport element (RTE), present in a subclass of rodent intracisteRNAl A particle retroelements (F. Nappi, R. Schneider, A. Zolotukhin, S. Smulevitch, D. Michalowski, J. Bear, B. Felber, and G. Pavlakis, J. Virol. 75:4558-4569, 2001), that is able to replace Rev-responsive element regulation in human immunodeficiency virus type 1. RTE-directed mRNA export is mediated by a still-unknown cellular factor(s), is independent of the CRM1 nuclear export receptor, and is conserved among vertebrates. Here we show that this RTE folds into an extended RNA secondary structure and thus does not resemble any known RTEs. Computer searches revealed the presence of 105 identical elements and more than 3,000 related elements which share at least 70% sequence identity with the RTE and which are found on all mouse chromosomes. These related elements are predicted to fold into RTE-like structures. Comparison of the sequences and structures revealed that the RTE and related elements can be divided into four groups. Mutagenesis of the RTE revealed that the minimal element contains four inteRNAl stem-loops, which are indispensable for function in mammalian cells. In contrast, only part of the element is essential to mediate RNA Transport in microinjected Xenopus laevis oocyte nuclei. Importantly, the minimal RTE able to promote RNA Transport has key structural features which are preserved in all the RTE-related elements, further supporting their functional importance. Therefore, RTE function depends on a complex secondary structure that is important for the interaction with the cellular export factor(s).
Jenifer Bear - One of the best experts on this subject based on the ideXlab platform.
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The RNA Transport Element of the Murine musD Retrotransposon Requires Long-range Intramolecular Interactions for Function
The Journal of biological chemistry, 2010Co-Authors: Michal Legiewicz, Andrei S. Zolotukhin, Guy R. Pilkington, Katarzyna J. Purzycka, Michelle Mitchell, Hiroaki Uranishi, Jenifer Bear, George N. Pavlakis, Stuart F. J. Le Grice, Barbara K. FelberAbstract:Abstract Retrovirus replication requires specialized Transport mechanisms to export genomic mRNA from the nucleus to the cytoplasm of the infected cell. This regulation is mediated by a combination of viral and/or cellular factors that interact with cis-acting RNA export elements linking the viral RNA to the cellular CRM1 or NXF1 nuclear export pathways. Endogenous type D murine LTR retrotransposons (musD) were reported to contain an RNA export element located upstream of the 3′-LTR. Although functionally equivalent, the musD export element, termed the musD Transport element, is distinct from the other retroviral RNA export elements, such as the constitutive Transport element of simian/Mason-Pfizer monkey retroviruses and the RNA Transport element found in rodent intracisteRNAl A-particle LTR retrotransposons. We demonstrate here that the minimal RNA Transport element (musD Transport element) of musD comprises multiple secondary structure elements that presumably serve as recognition signals for the cellular export machinery. We identified two classes of tertiary interactions, namely kissing loops and a pseudoknot. This work constitutes the first example of an RNA Transport element requiring such structural motifs to mediate nuclear export.
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The RNA Transport element RTE is essential for IAP LTR-retrotransposon mobility.
Virology, 2008Co-Authors: Andrei S. Zolotukhin, Hiroaki Uranishi, Jenifer Bear, George N. Pavlakis, Sergey Smulevitch, Daniel Michalowski, Ralf Schneider, Irina Tretyakova, Sean O'keeffe, Barbara K. FelberAbstract:We previously identified an RNA Transport element (RTE) present at a high copy number in the mouse genome. Here, we show that a related element, RTE-D, is part of a mobile LTR-retrotransposon, which belongs to a family of intracisteRNAl A-particle related elements (IAP). We demonstrate that RTE-D is essential for the mobility of the retrotransposon and it can be substituted by other known RNA export signals. RTE-deficient IAP transcripts are retained in the nucleus, while the RTE-containing transcripts accumulate in the cytoplasm allowing Gag protein expression. RTE-D acts as a posttranscriptional control element in a heterologous reporter mRNA and is activated by the cellular RNA binding protein 15 (RBM15), as reported for the previously described RTE. We identified a complex family of RTE-containing IAPs in mouse and mapped the active RTE-D-containing IAPs to the Mmr10 group of LTR-retrotransposons. These data reveal that, despite a complex evolutionary history, retroelements and retroviruses share the dependency on posttranscriptional regulation.
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RNA-binding motif protein 15 binds to the RNA Transport element RTE and provides a direct link to the NXF1 export pathway.
The Journal of biological chemistry, 2006Co-Authors: Susan Lindtner, Andrei S. Zolotukhin, Hiroaki Uranishi, Jenifer Bear, Barbara K. Felber, Sergey Smulevitch, Viraj Kulkarni, Martina Samiotaki, George Panayotou, George N. PavlakisAbstract:Retroviruses/retroelements provide tools enabling the identification and dissection of basic steps for post-transcriptional regulation of cellular mRNAs. The RNA Transport element (RTE) identified in mouse retrotransposons is functionally equivalent to constitutive Transport element of Type D retroviruses, yet does not bind directly to the mRNA export receptor NXF1. Here, we report that the RNA-binding motif protein 15 (RBM15) recognizes RTE directly and specifically in vitro and stimulates export and expression of RTE-containing reporter mRNAs in vivo. Tethering of RBM15 to a reporter mRNA showed that RBM15 acts by promoting mRNA export from the nucleus. We also found that RBM15 binds to NXF1 and the two proteins cooperate in stimulating RTE-mediated mRNA export and expression. Thus, RBM15 is a novel mRNA export factor and is part of the NXF1 pathway. We propose that RTE evolved as a high affinity RBM15 ligand to provide a splicing-independent link to NXF1, thereby ensuring efficient nuclear export and expression of retrotransposon transcripts.
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Structural and Functional Analysis of the RNA Transport Element, a Member of an Extensive Family Present in the Mouse Genome
Journal of virology, 2005Co-Authors: Sergey Smulevitch, Andrei S. Zolotukhin, Jenifer Bear, George N. Pavlakis, Daniel Michalowski, Ralf Schneider, Patricia Roth, Barbara K. FelberAbstract:We previously identified an RNA Transport element (RTE), present in a subclass of rodent intracisteRNAl A particle retroelements (F. Nappi, R. Schneider, A. Zolotukhin, S. Smulevitch, D. Michalowski, J. Bear, B. Felber, and G. Pavlakis, J. Virol. 75:4558-4569, 2001), that is able to replace Rev-responsive element regulation in human immunodeficiency virus type 1. RTE-directed mRNA export is mediated by a still-unknown cellular factor(s), is independent of the CRM1 nuclear export receptor, and is conserved among vertebrates. Here we show that this RTE folds into an extended RNA secondary structure and thus does not resemble any known RTEs. Computer searches revealed the presence of 105 identical elements and more than 3,000 related elements which share at least 70% sequence identity with the RTE and which are found on all mouse chromosomes. These related elements are predicted to fold into RTE-like structures. Comparison of the sequences and structures revealed that the RTE and related elements can be divided into four groups. Mutagenesis of the RTE revealed that the minimal element contains four inteRNAl stem-loops, which are indispensable for function in mammalian cells. In contrast, only part of the element is essential to mediate RNA Transport in microinjected Xenopus laevis oocyte nuclei. Importantly, the minimal RTE able to promote RNA Transport has key structural features which are preserved in all the RTE-related elements, further supporting their functional importance. Therefore, RTE function depends on a complex secondary structure that is important for the interaction with the cellular export factor(s).
Sergey Smulevitch - One of the best experts on this subject based on the ideXlab platform.
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The RNA Transport element RTE is essential for IAP LTR-retrotransposon mobility.
Virology, 2008Co-Authors: Andrei S. Zolotukhin, Hiroaki Uranishi, Jenifer Bear, George N. Pavlakis, Sergey Smulevitch, Daniel Michalowski, Ralf Schneider, Irina Tretyakova, Sean O'keeffe, Barbara K. FelberAbstract:We previously identified an RNA Transport element (RTE) present at a high copy number in the mouse genome. Here, we show that a related element, RTE-D, is part of a mobile LTR-retrotransposon, which belongs to a family of intracisteRNAl A-particle related elements (IAP). We demonstrate that RTE-D is essential for the mobility of the retrotransposon and it can be substituted by other known RNA export signals. RTE-deficient IAP transcripts are retained in the nucleus, while the RTE-containing transcripts accumulate in the cytoplasm allowing Gag protein expression. RTE-D acts as a posttranscriptional control element in a heterologous reporter mRNA and is activated by the cellular RNA binding protein 15 (RBM15), as reported for the previously described RTE. We identified a complex family of RTE-containing IAPs in mouse and mapped the active RTE-D-containing IAPs to the Mmr10 group of LTR-retrotransposons. These data reveal that, despite a complex evolutionary history, retroelements and retroviruses share the dependency on posttranscriptional regulation.
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RNA-binding motif protein 15 binds to the RNA Transport element RTE and provides a direct link to the NXF1 export pathway.
The Journal of biological chemistry, 2006Co-Authors: Susan Lindtner, Andrei S. Zolotukhin, Hiroaki Uranishi, Jenifer Bear, Barbara K. Felber, Sergey Smulevitch, Viraj Kulkarni, Martina Samiotaki, George Panayotou, George N. PavlakisAbstract:Retroviruses/retroelements provide tools enabling the identification and dissection of basic steps for post-transcriptional regulation of cellular mRNAs. The RNA Transport element (RTE) identified in mouse retrotransposons is functionally equivalent to constitutive Transport element of Type D retroviruses, yet does not bind directly to the mRNA export receptor NXF1. Here, we report that the RNA-binding motif protein 15 (RBM15) recognizes RTE directly and specifically in vitro and stimulates export and expression of RTE-containing reporter mRNAs in vivo. Tethering of RBM15 to a reporter mRNA showed that RBM15 acts by promoting mRNA export from the nucleus. We also found that RBM15 binds to NXF1 and the two proteins cooperate in stimulating RTE-mediated mRNA export and expression. Thus, RBM15 is a novel mRNA export factor and is part of the NXF1 pathway. We propose that RTE evolved as a high affinity RBM15 ligand to provide a splicing-independent link to NXF1, thereby ensuring efficient nuclear export and expression of retrotransposon transcripts.
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Structural and Functional Analysis of the RNA Transport Element, a Member of an Extensive Family Present in the Mouse Genome
Journal of virology, 2005Co-Authors: Sergey Smulevitch, Andrei S. Zolotukhin, Jenifer Bear, George N. Pavlakis, Daniel Michalowski, Ralf Schneider, Patricia Roth, Barbara K. FelberAbstract:We previously identified an RNA Transport element (RTE), present in a subclass of rodent intracisteRNAl A particle retroelements (F. Nappi, R. Schneider, A. Zolotukhin, S. Smulevitch, D. Michalowski, J. Bear, B. Felber, and G. Pavlakis, J. Virol. 75:4558-4569, 2001), that is able to replace Rev-responsive element regulation in human immunodeficiency virus type 1. RTE-directed mRNA export is mediated by a still-unknown cellular factor(s), is independent of the CRM1 nuclear export receptor, and is conserved among vertebrates. Here we show that this RTE folds into an extended RNA secondary structure and thus does not resemble any known RTEs. Computer searches revealed the presence of 105 identical elements and more than 3,000 related elements which share at least 70% sequence identity with the RTE and which are found on all mouse chromosomes. These related elements are predicted to fold into RTE-like structures. Comparison of the sequences and structures revealed that the RTE and related elements can be divided into four groups. Mutagenesis of the RTE revealed that the minimal element contains four inteRNAl stem-loops, which are indispensable for function in mammalian cells. In contrast, only part of the element is essential to mediate RNA Transport in microinjected Xenopus laevis oocyte nuclei. Importantly, the minimal RTE able to promote RNA Transport has key structural features which are preserved in all the RTE-related elements, further supporting their functional importance. Therefore, RTE function depends on a complex secondary structure that is important for the interaction with the cellular export factor(s).
