The Experts below are selected from a list of 27606 Experts worldwide ranked by ideXlab platform
Woanyuh Tarn - One of the best experts on this subject based on the ideXlab platform.
-
rna binding motif protein 4 translocates to cytoplasmic granules and suppresses translation via argonaute2 during muscle cell differentiation
Journal of Biological Chemistry, 2009Co-Authors: Jung Chun Lin, Woanyuh TarnAbstract:The RNA-binding motif protein 4 (RBM4) plays multiple roles in mRNA metabolism, including translation control. RBM4 suppresses cap-dependent translation but activates internal ribosome entry site-mediated translation. Because of its high expression level in muscle and heart, we investigated the function of RBM4 in myoblast cells. Here, we demonstrate that RBM4 is phosphorylated and translocates to the cytoplasm in mouse C2C12 cells upon cell differentiation. Notably, RBM4 is transiently deposited into cytoplasmic granules containing microtubule assembly factors as well as poly(A)+ RNAs. Moreover, RBM4 colocalizes with the components of micro-Ribonucleoproteins, including the Argonaute2 (Ago2) protein, during muscle cell differentiation. RBM4 interacts directly with Ago2 and may recruit Ago2 to suppress translation of target mRNAs. Furthermore, RBM4 selectively associates with muscle cell-specific microRNAs and potentiates their translation repression activity by promoting micro-Ribonucleoprotein association with target mRNAs. Altogether, our results suggest that RBM4 translocates to the cytoplasm and participates in translation suppression during muscle cell differentiation.
-
the dead box rna helicase ddx3 associates with export messenger Ribonucleoproteins as well astip associated protein and participates in translational control
Molecular Biology of the Cell, 2008Co-Authors: Woanyuh TarnAbstract:Nuclear export of mRNA is tightly linked to transcription, nuclear mRNA processing, and subsequent maturation in the cytoplasm. Tip-associated protein (TAP) is the major nuclear mRNA export receptor, and it acts coordinately with various factors involved in mRNA expression. We screened for protein factors that associate with TAP and identified several candidates, including RNA helicase DDX3. We demonstrate that DDX3 directly interacts with TAP and that its association with TAP as well as mRNA Ribonucleoprotein complexes may occur in the nucleus. Depletion of TAP resulted in nuclear accumulation of DDX3, suggesting that DDX3 is, at least in part, exported along with messenger Ribonucleoproteins to the cytoplasm via the TAP-mediated pathway. Moreover, the observation that DDX3 localizes transiently in cytoplasmic stress granules under cell stress conditions suggests a role for DDX3 in translational control. Indeed, DDX3 associates with translation initiation complexes. However, DDX3 is probably not critical for general mRNA translation but may instead promote efficient translation of mRNAs containing a long or structured 5′ untranslated region. Given that the DDX3 RNA helicase activity is essential for its involvement in translation, we suggest that DDX3 facilitates translation by resolving secondary structures of the 5′-untranslated region in mRNAs during ribosome scanning.
-
the dead box rna helicase ddx3 associates with export messenger Ribonucleoproteins as well as tip associated protein and participates in translational control
Molecular Biology of the Cell, 2008Co-Authors: Mingchih Lai, Woanyuh Tarn, Yanhwa Wu LeeAbstract:Nuclear export of mRNA is tightly linked to transcription, nuclear mRNA processing, and subsequent maturation in the cytoplasm. Tip-associated protein (TAP) is the major nuclear mRNA export receptor, and it acts coordinately with various factors involved in mRNA expression. We screened for protein factors that associate with TAP and identified several candidates, including RNA helicase DDX3. We demonstrate that DDX3 directly interacts with TAP and that its association with TAP as well as mRNA Ribonucleoprotein complexes may occur in the nucleus. Depletion of TAP resulted in nuclear accumulation of DDX3, suggesting that DDX3 is, at least in part, exported along with messenger Ribonucleoproteins to the cytoplasm via the TAP-mediated pathway. Moreover, the observation that DDX3 localizes transiently in cytoplasmic stress granules under cell stress conditions suggests a role for DDX3 in translational control. Indeed, DDX3 associates with translation initiation complexes. However, DDX3 is probably not critical for general mRNA translation but may instead promote efficient translation of mRNAs containing a long or structured 5' untranslated region. Given that the DDX3 RNA helicase activity is essential for its involvement in translation, we suggest that DDX3 facilitates translation by resolving secondary structures of the 5'-untranslated region in mRNAs during ribosome scanning.
Juan Ortín - One of the best experts on this subject based on the ideXlab platform.
-
the influenza virus rna synthesis machine advances in its structure and function
RNA Biology, 2011Co-Authors: Patricia Resainfante, Nuria Jorba, R Coloma, Juan OrtínAbstract:The influenza A viruses are the causative agents of respiratory disease that occurs as yearly epidemics and occasional pandemics. These viruses are endemic in wild avian species and can sometimes break the species barrier to infect and generate new virus lineages in humans. The influenza A virus genome consists of eight single-stranded, negative-polarity RNAs that form Ribonucleoprotein complexes by association to the RNA polymerase and the nucleoprotein. In this review we focus on the structure of this RNA-synthesis machines and the included RNA polymerase, and on the mechanisms by which they express their genetic information as mRNAs and generate progeny Ribonucleoproteins that will become incorporated into new infectious virions. New structural, biochemical and genetic data are rapidly accumulating in this very active area of research. We discuss these results and attempt to integrate the information into structural and functional models that may help the design of new experiments and further our knowledge on virus RNA replication and gene expression. This interplay between structural and functional data will eventually provide new targets for controlled attenuation or antiviral therapy.
-
the influenza virus rna synthesis machine advances in its structure and function
RNA Biology, 2011Co-Authors: Patricia Resainfante, Nuria Jorba, R Coloma, Juan OrtínAbstract:The influenza A viruses are the causative agents of respiratory disease that occurs as yearly epidemics and occasional pandemics. These viruses are endemic in wild avian species and can sometimes break the species barrier to infect and generate new virus lineages in humans. The influenza A virus genome consists of eight single-stranded, negative-polarity RNAs that form Ribonucleoprotein complexes by association to the RNA polymerase and the nucleoprotein. In this review we focus on the structure of this RNA-synthesis machines and the included RNA polymerase, and on the mechanisms by which they express their genetic information as mRNAs and generate progeny Ribonucleoproteins that will become incorporated into new infectious virions. New structural, biochemical and genetic data are rapidly accumulating in this very active area of research. We discuss these results and attempt to integrate the information into structural and functional models that may help the design of new experiments and further our knowl...
-
Three-dimensional reconstruction of a recombinant influenza virus Ribonucleoprotein particle.
EMBO reports, 2001Co-Authors: Jaime Martín-benito, Estela Area, Joaquin Ortega, Oscar Llorca, José M. Valpuesta, José L. Carrascosa, Juan OrtínAbstract:A three-dimensional structural model of an influenza virus Ribonucleoprotein particle reconstituted in vivo from recombinant proteins and a model genomic vRNA has been generated by electron microscopy. It shows a circular shape and contains nine nucleoprotein monomers, two of which are connected with the polymerase complex. The nucleoprotein monomers show a curvature that may be responsible for the formation of helical structures in the full-size viral Ribonucleoproteins. The monomers show distinct contact boundaries at the two sides of the particle, suggesting that the genomic RNA may be located in association with the nucleoprotein at the base of the Ribonucleoprotein complex. Sections of the three-dimensional model show a trilobular morphology in the polymerase complex that is consistent with the presence of its three subunits.
Mark T Mcnally - One of the best experts on this subject based on the ideXlab platform.
-
heterogeneous nuclear Ribonucleoprotein h is required for optimal u11 small nuclear Ribonucleoprotein binding to a retroviral rna processing control element implications for u12 dependent rna splicing
Journal of Biological Chemistry, 2006Co-Authors: Lisa M Mcnally, Lily Yee, Mark T McnallyAbstract:Next Section Abstract An RNA-processing element from Rous sarcoma virus, the negative regulator of splicing (NRS), represses splicing to generate unspliced RNA that serves as mRNA and as genomic RNA for progeny virions and also promotes polyadenylation of the unspliced RNA. Integral to NRS function is the binding of U1 small nuclear Ribonucleoprotein (snRNP), but its binding is controlled by U11 snRNP that binds to an overlapping site. U11 snRNP, the U1 counterpart for splicing of U12-dependent introns, binds the NRS remarkably well and requires G-rich elements just downstream of the consensus U11 binding site. We present evidence that heterogeneous nuclear Ribonucleoprotein (hnRNP) H binds to the NRS G-rich elements and that hnRNP H is required for optimal U11 binding in vitro. It is further shown that hnRNP H (but not hnRNP F) can promote U11 binding and splicing from the NRS in vivo when tethered to the RNA as an MS2 fusion protein. Interestingly, 17% of the naturally occurring U12-dependent introns have at least two potential hnRNP H binding sites positioned similarly to the NRS. For two such introns from the SCN4A and P120 genes, we show that hnRNP H binds to each in a G-tract-dependent manner, that G-tract mutations strongly reduce splicing of minigene RNA, and that tethered hnRNP H restores splicing to mutant RNA. In support of a role for hnRNP H in both splicing pathways, hnRNP H antibodies co-precipitate U1 and U11 small nuclear Ribonucleoproteins. These results indicate that hnRNP H is an auxiliary factor for U11 binding to the NRS and that, more generally, hnRNP H is a splicing factor for a subset of U12-dependent introns that harbor G-rich elements.
-
heterogeneous nuclear Ribonucleoprotein h is required for optimal u11 small nuclear Ribonucleoprotein binding to a retroviral rna processing control element implications for u12 dependent rna splicing
Journal of Biological Chemistry, 2006Co-Authors: Lisa M Mcnally, Lily Yee, Mark T McnallyAbstract:An RNA-processing element from Rous sarcoma virus, the negative regulator of splicing (NRS), represses splicing to generate unspliced RNA that serves as mRNA and as genomic RNA for progeny virions and also promotes polyadenylation of the unspliced RNA. Integral to NRS function is the binding of U1 small nuclear Ribonucleoprotein (snRNP), but its binding is controlled by U11 snRNP that binds to an overlapping site. U11 snRNP, the U1 counterpart for splicing of U12-dependent introns, binds the NRS remarkably well and requires G-rich elements just downstream of the consensus U11 binding site. We present evidence that heterogeneous nuclear Ribonucleoprotein (hnRNP) H binds to the NRS G-rich elements and that hnRNP H is required for optimal U11 binding in vitro. It is further shown that hnRNP H (but not hnRNP F) can promote U11 binding and splicing from the NRS in vivo when tethered to the RNA as an MS2 fusion protein. Interestingly, 17% of the naturally occurring U12-dependent introns have at least two potential hnRNP H binding sites positioned similarly to the NRS. For two such introns from the SCN4A and P120 genes, we show that hnRNP H binds to each in a G-tract-dependent manner, that G-tract mutations strongly reduce splicing of minigene RNA, and that tethered hnRNP H restores splicing to mutant RNA. In support of a role for hnRNP H in both splicing pathways, hnRNP H antibodies co-precipitate U1 and U11 small nuclear Ribonucleoproteins. These results indicate that hnRNP H is an auxiliary factor for U11 binding to the NRS and that, more generally, hnRNP H is a splicing factor for a subset of U12-dependent introns that harbor G-rich elements.
Lisa M Mcnally - One of the best experts on this subject based on the ideXlab platform.
-
heterogeneous nuclear Ribonucleoprotein h is required for optimal u11 small nuclear Ribonucleoprotein binding to a retroviral rna processing control element implications for u12 dependent rna splicing
Journal of Biological Chemistry, 2006Co-Authors: Lisa M Mcnally, Lily Yee, Mark T McnallyAbstract:Next Section Abstract An RNA-processing element from Rous sarcoma virus, the negative regulator of splicing (NRS), represses splicing to generate unspliced RNA that serves as mRNA and as genomic RNA for progeny virions and also promotes polyadenylation of the unspliced RNA. Integral to NRS function is the binding of U1 small nuclear Ribonucleoprotein (snRNP), but its binding is controlled by U11 snRNP that binds to an overlapping site. U11 snRNP, the U1 counterpart for splicing of U12-dependent introns, binds the NRS remarkably well and requires G-rich elements just downstream of the consensus U11 binding site. We present evidence that heterogeneous nuclear Ribonucleoprotein (hnRNP) H binds to the NRS G-rich elements and that hnRNP H is required for optimal U11 binding in vitro. It is further shown that hnRNP H (but not hnRNP F) can promote U11 binding and splicing from the NRS in vivo when tethered to the RNA as an MS2 fusion protein. Interestingly, 17% of the naturally occurring U12-dependent introns have at least two potential hnRNP H binding sites positioned similarly to the NRS. For two such introns from the SCN4A and P120 genes, we show that hnRNP H binds to each in a G-tract-dependent manner, that G-tract mutations strongly reduce splicing of minigene RNA, and that tethered hnRNP H restores splicing to mutant RNA. In support of a role for hnRNP H in both splicing pathways, hnRNP H antibodies co-precipitate U1 and U11 small nuclear Ribonucleoproteins. These results indicate that hnRNP H is an auxiliary factor for U11 binding to the NRS and that, more generally, hnRNP H is a splicing factor for a subset of U12-dependent introns that harbor G-rich elements.
-
heterogeneous nuclear Ribonucleoprotein h is required for optimal u11 small nuclear Ribonucleoprotein binding to a retroviral rna processing control element implications for u12 dependent rna splicing
Journal of Biological Chemistry, 2006Co-Authors: Lisa M Mcnally, Lily Yee, Mark T McnallyAbstract:An RNA-processing element from Rous sarcoma virus, the negative regulator of splicing (NRS), represses splicing to generate unspliced RNA that serves as mRNA and as genomic RNA for progeny virions and also promotes polyadenylation of the unspliced RNA. Integral to NRS function is the binding of U1 small nuclear Ribonucleoprotein (snRNP), but its binding is controlled by U11 snRNP that binds to an overlapping site. U11 snRNP, the U1 counterpart for splicing of U12-dependent introns, binds the NRS remarkably well and requires G-rich elements just downstream of the consensus U11 binding site. We present evidence that heterogeneous nuclear Ribonucleoprotein (hnRNP) H binds to the NRS G-rich elements and that hnRNP H is required for optimal U11 binding in vitro. It is further shown that hnRNP H (but not hnRNP F) can promote U11 binding and splicing from the NRS in vivo when tethered to the RNA as an MS2 fusion protein. Interestingly, 17% of the naturally occurring U12-dependent introns have at least two potential hnRNP H binding sites positioned similarly to the NRS. For two such introns from the SCN4A and P120 genes, we show that hnRNP H binds to each in a G-tract-dependent manner, that G-tract mutations strongly reduce splicing of minigene RNA, and that tethered hnRNP H restores splicing to mutant RNA. In support of a role for hnRNP H in both splicing pathways, hnRNP H antibodies co-precipitate U1 and U11 small nuclear Ribonucleoproteins. These results indicate that hnRNP H is an auxiliary factor for U11 binding to the NRS and that, more generally, hnRNP H is a splicing factor for a subset of U12-dependent introns that harbor G-rich elements.
Graeme I. Murray - One of the best experts on this subject based on the ideXlab platform.
-
the expression profile of rna binding proteins in primary and metastatic colorectal cancer relationship of heterogeneous nuclear Ribonucleoproteins with prognosis
Human Pathology, 2011Co-Authors: Nicholas R. Hope, Graeme I. MurrayAbstract:Summary The heterogeneous nuclear Ribonucleoproteins are a group of RNA-binding proteins with a range of key cellular functions, which are dysregulated in tumorigenesis including regulation of translational and RNA processing. The aims of this study were to define the heterogeneous nuclear Ribonucleoprotein expression profile in primary and metastatic colorectal cancer and to establish the clinicopathologic significance of this expression. A tissue microarray containing 515 primary colorectal cancers, 224 lymph node metastasis of colorectal cancer, and 50 normal colon samples was immunostained for 6 heterogeneous nuclear Ribonucleoproteins. Heterogeneous nuclear Ribonucleoprotein I, heterogeneous nuclear Ribonucleoprotein K, and heterogeneous nuclear Ribonucleoprotein L displayed the most frequent strong immunoreactivity in primary colorectal tumor samples. Heterogeneous nuclear Ribonucleoprotein A1 ( P P = .003) showed significant alterations in nuclear expression in tumors compared with normal colonic epithelium, whereas heterogeneous nuclear Ribonucleoprotein A1 ( P = .001), heterogeneous nuclear Ribonucleoprotein I ( P P P = .001), heterogeneous nuclear Ribonucleoprotein I ( P P = .001). Nuclear heterogeneous nuclear Ribonucleoprotein H ( χ 2 = 72.1; P χ 2 = 28.1; P χ 2 = 13.2; P = .04) all showed significant associations with tumor stage. There was a significant relationship between strong nuclear heterogeneous nuclear Ribonucleoprotein H expression and survival ( χ 2 = 14.97; P
-
The expression profile of RNA-binding proteins in primary and metastatic colorectal cancer: relationship of heterogeneous nuclear Ribonucleoproteins with prognosis.
Human pathology, 2010Co-Authors: Nicholas R. Hope, Graeme I. MurrayAbstract:The heterogeneous nuclear Ribonucleoproteins are a group of RNA-binding proteins with a range of key cellular functions, which are dysregulated in tumorigenesis including regulation of translational and RNA processing. The aims of this study were to define the heterogeneous nuclear Ribonucleoprotein expression profile in primary and metastatic colorectal cancer and to establish the clinicopathologic significance of this expression. A tissue microarray containing 515 primary colorectal cancers, 224 lymph node metastasis of colorectal cancer, and 50 normal colon samples was immunostained for 6 heterogeneous nuclear Ribonucleoproteins. Heterogeneous nuclear Ribonucleoprotein I, heterogeneous nuclear Ribonucleoprotein K, and heterogeneous nuclear Ribonucleoprotein L displayed the most frequent strong immunoreactivity in primary colorectal tumor samples. Heterogeneous nuclear Ribonucleoprotein A1 (P < .001) and heterogeneous nuclear Ribonucleoprotein U (P = .003) showed significant alterations in nuclear expression in tumors compared with normal colonic epithelium, whereas heterogeneous nuclear Ribonucleoprotein A1 (P = .001), heterogeneous nuclear Ribonucleoprotein I (P < .001), and heterogeneous nuclear Ribonucleoprotein K (P < .001) all showed significant aberrant cytoplasmic immunoreactivity in tumor cells. There were also significant differences in cytoplasmic immunoreactivity between the primary tumor and the corresponding lymph node metastasis for heterogeneous nuclear Ribonucleoprotein A1 (P = .001), heterogeneous nuclear Ribonucleoprotein I (P < .001), and heterogeneous nuclear Ribonucleoprotein K (P = .001). Nuclear heterogeneous nuclear Ribonucleoprotein H (χ(2) = 72.1; P < .001), cytoplasmic heterogeneous nuclear Ribonucleoprotein I (χ(2) = 28.1; P < .001), and cytoplasmic heterogeneous nuclear Ribonucleoprotein K (χ(2) = 13.2; P = .04) all showed significant associations with tumor stage. There was a significant relationship between strong nuclear heterogeneous nuclear Ribonucleoprotein H expression and survival (χ(2) = 14.97; P < .001). This study has defined the expression profile of heterogeneous nuclear Ribonucleoproteins in colorectal cancer and shown that there are significant alterations in both expression and subcellular localization of individual heterogeneous nuclear Ribonucleoproteins in this type of tumor.
