Abstract: This invention provides compounds that inhibit p38 mitogen-activated protein kinase. Moreover, the invention provides methods for testing a candidate compound for a p38 mitogen-activated protein kinase modifying activity by calculating the level of relocalization of an SMN complex component from the cytoplasm to the nucleus of a cell. Additionally, the invention provides a kit and a system for calculating the same.

Abstract: The invention provides a method of regulating U1 activity associated with its splicing role as well as its role in protecting pre-mRNAs from premature termination by cleavage and polyadenylation, thereby modulating expression of a gene or genes. In one embodiment, the invention includes compositions and methods for regulating gene expression and treating diseases associated with dysregulated gene expression.

Abstract: This invention provides compounds that inhibit p38 mitogen-activated protein kinase. Moreover, the invention provides methods for testing a candidate compound for a p38 mitogen-activated protein kinase modifying activity by calculating the level of relocalization of an SMN complex component from the cytoplasm to the nucleus of a cell. Additionally, the invention provides a kit and a system for calculating the same.

Abstract: The invention provides a method of regulating U1 activity associated with its splicing role as well as its role in protecting pre-mRNAs from premature termination by cleavage and polyadenylation, thereby modulating expression of a gene or genes. In one embodiment, the invention includes compositions and methods for regulating gene expression and treating diseases associated with dysregulated gene expression.

Abstract: This invention provides methods for treating diseases associated with elevated p38 mitogen-activated protein kinase activity. Moreover, the invention provides methods for testing a candidate compound for a p38 mitogen-activated protein kinase modifying activity by calculating the level of relocalization of an SMN complex component from the cytoplasm to the nucleus of a cell. Additionally, the invention provides a kit and a system for calculating the same.

Abstract: This invention provides methods for treating diseases associated with elevated p38 mitogen-activated protein kinase activity. Moreover, the invention provides methods for testing a candidate compound for a p38 mitogen-activated protein kinase modifying activity by calculating the level of relocalization of an SMN complex component from the cytoplasm to the nucleus of a cell. Additionally, the invention provides a kit and a system for calculating the same.

Abstract: This invention provides methods for treating diseases associated with elevated p38 mitogen-activated protein kinase activity. Moreover, the invention provides methods for testing a candidate compound for a p38 mitogen-activated protein kinase modifying activity by calculating the level of relocalization of an SMN complex component from the cytoplasm to the nucleus of a cell. Additionally, the invention provides a kit and a system for calculating the same.

Abstract: The present invention is based on the discovery of a cell-based system to identify novel modulators of splicing or splicing dependent processes. The cell-based system of the present invention utilizes a fast and highly sensitive reporter, that responds to defects in the splicing machinery itself and is sensitive to changes in the signals that regulate splicing dependent processes such as those that modulate the EJC, splicing-dependent export, localization or translation efficiency. The present invention further uses the cell-based screen to identify several small molecules that modulate both constitutive and alternative splicing. Accordingly, the present invention includes general or alternative splicing inhibitors identified using the assay described herein. The present invention also provides methods of treating a subject having a condition associated with aberrant target RNA expression.

Abstract: The present invention relates to the discovery of a novel global gene expression regulation mechanism whereby U1 snRNP (U1) protects pre-mRNAs. In one embodiment, the invention includes compositions and methods for regulating gene expression and treating diseases associated with dysregulated gene expression.

Abstract: The present invention includes methods for modulating the expression of a gene or mRNA in a cell using small nuclear RNAs comprising specific sequence and structural features and further comprising a nucleic acid cargo.

Abstract: The present invention includes an isolated nucleic acid comprising a nucleic acid sequence encoding a SMN?7 degron and the encoded polypeptide. The invention also includes inhibitors of SMN?7 degron. The invention also includes compositions and methods for mitigating SMN deficiency by targeting inhibition of factors that mediate SMN?7-degron dependent degradation of SMN?7.

Abstract: The present invention includes assays and kits for detecting the assembly of an RNA binding protein-RNA complex and for detecting the activity of an RNA binding protein.

Abstract: This invention provides methods for screening an inhibitor of protein synthesis by measuring the level of relocalization of an SMN complex component from the cytoplasm to the nucleus. Additionally, the invention provides a kit and a system for screening protein synthesis inhibitors in a cell.

Abstract: The present invention includes an isolated nucleic acid comprising a nucleic acid sequence encoding a SMN?7 degron and the encoded polypeptide. The invention also includes inhibitors of SMN?7 degron. The invention also includes compositions and methods for mitigating SMN deficiency by targeting inhibition of factors that mediate SMN?7-degron dependent degradation of SMN?7.

Abstract: This invention provides methods for screening an inhibitor of protein synthesis by measuring the level of relocalization of an SMN complex component from the cytoplasm to the nucleus. Additionally, the invention provides a kit and a system for screening protein synthesis inhibitors in a cell.

Abstract: This invention provides methods for screening an inhibitor of protein synthesis by measuring the level of relocalization of an SMN complex component from the cytoplasm to the nucleus. Additionally, the invention provides a kit and a system for screening protein synthesis inhibitors in a cell.

Abstract: The present invention is based on the discovery of a cell-based system to identify novel modulators of splicing or splicing dependent processes. The cell-based system of the present invention utilizes a fast and highly sensitive reporter, that responds to defects in the splicing machinery itself and is sensitive to changes in the signals that regulate splicing dependent processes such as those that modulate the EJC, splicing-dependent export, localization or translation efficiency. The present invention further uses the cell-based screen to identify several small molecules that modulate both constitutive and alternative splicing. Accordingly, the present invention includes general or alternative splicing inhibitors identified using the assay described herein. The present invention also provides methods of treating a subject having a condition associated with aberrant target RNA expression.

Abstract: The present invention provides methods for treating neurological diseases and disorders. Compounds that replace or enhance the function of SMN or alleviate or reduce a phenotype of cells with low SMN protein levels are provided. Screening methods and kits for identifying such compounds also are provided.

Abstract: This invention provides methods for treating diseases associated with elevated p38 mitogen-activated protein kinase activity. Moreover, the invention provides methods for testing a candidate compound for a p38 mitogen-activated protein kinase modifying activity by calculating the level of relocalization of an SMN complex component from the cytoplasm to the nucleus of a cell. Additionally, the invention provides a kit and a system for calculating the same.

Abstract: This invention provides methods for screening an inhibitor of protein synthesis by measuring the level of relocalization of an SMN complex component from the cytoplasm to the nucleus. Additionally, the invention provides a kit and a system for screening protein synthesis inhibitors in a cell.