Abstract: Provided herein are antiviral compounds having the structure of Formula (I) and compositions thereof for use in the treatment of viral infection. In particular, the compounds of Formula (I) are capable of interfering with the export of viral mRNA processing as reflected in the altered accumulation of viral RNA isoforms as well as transport from the nucleus to the cytoplasm. Such compounds show a reduction of HIV, adenovirus and coronavirus infection of cells. The invention provides compounds that may be suitable for the treatment of HIV/AIDS.

Abstract: In the present invention, the proteomic identification of HBc interacting factors in the nucleus of human hepatocytes revealed a majority of RNA-binding proteins (RBPs) intervening in mRNA metabolism and especially, the serine/arginine-rich splicing factor (10) (SRSF1O) which was found enriched nearly (3000) times in HBc complexes. Inventors demonstrated that the inhibition of SRSF1O phosphorylation with the small molecule 1C8 (4-pyridinonebenzisothiazole carboxamide) induces a strong inhibition of HBV replication (genotypes C and D) in persistently-infected hepatocytes, as well as to a strong inhibition of the establishment of HBV cccDNA in de novo infection settings. Accordingly the present invention relates to an inhibitor of SRSF1O activity for use in the treatment of Hepatitis B virus (HBV) infection said inhibitor maintain SRSF1O in a dephosphorylated state and prevents or reduces the splicing activity of SRSF1O.

Abstract: The present invention relates to a method of modulating splice site selection, splicing and alternative, the method comprising the step of hybridizing an oligonucleotide-protein conjugate to a target pre-mRNA molecule in a cell or cell extract, wherein the oligonucleotide-protein conjugate comprises an oligonucleotide moiety which comprises at least two distinct sequence elements: (i) a nucleic acid sequence that is complementary to a specific region upstream of the splice site in the target pre-mRNA molecule; and (ii) an extension containing a protein binding site sequence element for covalently binding a protein; wherein the protein moiety comprises a protein capable of modulating splicing of the splice site upon binding with the protein binding site.

Abstract: The present invention relates to the identification of secreted protein isoforms specific in ovarian cancer and methods for diagnosis or prognosis of ovarian cancer in a subject by detecting the secreted protein isoforms.

Abstract: The present invention relates to a method to identify alternatively spliced variants enriched in cancer specimens and a method for prognosis of cancer in a subject by detecting a signature of splicing events. There is also provided a method for profiling cancer in a subject by detecting a signature of splicing events.

Abstract: The present invention relates to a method of modulating splice site selection, splicing and alternative, the method comprising the step of hybridizing an oligonucleotide-protein conjugate to a target pre-mRNA molecule in a cell or cell extract, wherein the oligonucleotide-protein conjugate comprises an oligonucleotide moiety which comprises at least two distinct sequence elements: (i) a nucleic acid sequence that is complementary to a specific region upstream of the splice site in the target pre-mRNA molecule; and (ii) an extension containing a protein binding site sequence element for covalently binding a protein; wherein the protein moiety comprises a protein capable of modulating splicing of the splice site upon binding with the protein binding site.

Abstract: The present invention relates to a method of modulating splice site selection, splicing and alternative, the method comprising the step of hybridizing an oligonucleotide-protein conjugate to a target pre-mRNA molecule in a cell or cell extract, wherein the oligonucleotide-protein conjugate comprises an oligonucleotide moiety which comprises at least two distinct sequence elements: (i) a nucleic acid sequence that is complementary to a specific region upstream of the splice site in the target pre-mRNA molecule; and (ii) an extension containing a protein binding site sequence element for covalently binding a protein; wherein the protein moiety comprises a protein capable of modulating splicing of the splice site upon binding with the protein binding site.

Abstract: The present invention provides methods for inducing cell death using hnRNP A1, A1B, A2, and B1 nucleic acid molecules. The invention further provides therapeutic and diagnostic methods for neoplasia treatment relating to hnRNP A1, A1B, A2, and B1 nucleic acid molecules.

Abstract: The present invention relates to splicing and especially to alternative RNA splicing which is involved in the production of protein isoforms with distinct activities. More specifically, the present invention relates to methods for modulating alternative splicing, and for identifying alternatively spliced units in genes. The present invention also concerns methods for modulating the ratio of alternatively spliced isoforms relative to each other and to normalize the alternative splicing actions of a splicing extract. The invention also relates to kits for normalizing and/or modulating splicing and/or alternative splicing of transcripts. More particularly the invention relates to a method to normalize a splicing and/or alternative splicing activity of an extract comprising an addition thereto of an effective amount of a polar aprotic solvent, whereby the effective amount normalizes splicing and/or alternative splicing as compared to an untreated extract.

Abstract: The present invention relates to the length of telomeres and the role of hnRNP A1, UP1 or derivatives thereon. More particularly, the present invention relates to hnRNP A1, UP1 or derivatives thereof to maintain or alter the length of telomeres in cells. The present invention also relates to methods and compositions for increasing or decreasing the proliferative capacity of cells and to delay or precipitate the onset of senescence. The invention further relates to hnRNP A1 or UP1 or derivatives thereof as pharmaceutical, therapeutic and diagnostic reagents.

Abstract: The present invention relates to the length of telomeres and to their effect on proliferation and senescence in cells. More specifically, it concerns the ability of hnRNP A1 and its shortened derivative UP1 to alter the length of telomeres in cells. More precisely, the invention relates to the ability of A1/UP1 to bind telomerase RNA, to bind and to protect mammalian telomeric DNA, and to modulate telomere extension and replication. Finally, the present invention relates to agents which can interfere with the binding of A1/UP1 to telomeres and telomerase, and to the use of protection, extension and replication assays to measure the biological impact of these agents.

Abstract: The present invention relates to the length of telomeres and the role of hnRNP A1, UP1 or derivatives thereon. More particularly, the present invention relates to hnRNP A1, UP1 or derivatives thereof to maintain or alter the length of telomeres in cells. The present invention also relates to methods and compositions for increasing or decreasing the proliferative capacity of cells and to delay or precipitate the onset of senescence The invention further relates to hnRNP A1 or UP1 or derivatives thereof as pharmaceutical, therapeutic and diagnostic reagents.