Use of RBM39 as a biomaker
The present invention relates to the use (i) of a level of expression of a long RBM39 protein isoform, termed RBM39L, and (ii) of a level of expression of a short RBM39 protein isoform, termed RBM39C, as a marker for the efficacy of an active agent capable of preventing and/or treating HIV infection.
1. A method for evaluating the efficacy of an active substance suitable for preventing and/or treating an HIV infection comprising:
determining (i) an expression level of a long isoform of an RBM39 protein, called RBM39L, and
determining (ii) an expression level of a short isoform of an RBM39 protein, called RBM39S;
wherein a shift toward the expression level of the long isoform relative to the expression level of the short isoform is indicative of the efficacy of said active substance for preventing and/or treating the HIV infection.
2. The method as claimed in claim 1 , wherein said expression levels consist respectively of (i) a transcription level of an mRNA coding for a long isoform, called mRNA-L, and (ii) a transcription level of an mRNA coding for a short isoform, called mRNA-S, of an RBM39 protein.
3. The method as claimed in claim 1 , wherein said expression levels consist respectively of (i) a level of production of a long isoform, called ProtL, and (ii) a level of production of a short isoform, called ProtS, of an RBM39 protein.
4. The method as claimed in claim 1 , wherein a ratio of the expression level of RBM39L to the sum of the expression levels of RBM39L and of RBM39S is determined.
5. The method as claimed in claim 1 , wherein the expression levels consist of transcription levels and are determined by a technique of quantification with amplification of nucleic acids.
6. The method as claimed in claim 1 , wherein the expression levels consist of levels of production and are determined by a method of immunodetection.
7. A method of screening in vitro or ex vivo of an active substance that is presumed to prevent and/or treat an HIV infection comprising at least the steps consisting of:
a—bringing in contact:
i—at least one cell suitable for the transcription, by alternative splicing, of an mRNA coding for a long isoform, mRNA-L, and of an mRNA coding for a short isoform, mRNA-S, of the RBM39 protein, said cell being disposed in conditions that are favorable to said transcription, and
ii—an active substance to be screened,
in conditions favorable to observation of a possible effect of said active substance on the transcription of an RBM39 gene,
b—determining a transcription level of an mRNA-L and a transcription level of an mRNA-S of said RBM39 gene,
c—determining a ratio of the transcription levels determined in step b),
d—comparing said ratio obtained in step c) with a reference ratio;
wherein a shift toward the transcription level of the RBM39 gene toward the mRNA coding for the long isoform relative to the transcription level of the RBM39 gene toward the mRNA coding for the short isoform is indicative of the efficacy of said active substance for preventing and/or treating the HIV infection.
8. The method as claimed in claim 7 , wherein the ratio determined in step c) consists of the ratio of the transcription level of mRNA-L to the sum of the transcription levels of mRNA-L and mRNA-S.
9. The method as claimed in claim 7 , wherein a deviation between the ratio obtained in step c) and the reference ratio is indicative of a possible effect of said active substance to be tested.
10. The method as claimed in claim 7 , wherein said cell is selected from the peripheral blood mononuclear cells, or any other cells that may be infected by HIV.
11. The method as claimed in claim 7 , wherein the transcription levels of mRNA-L and mRNA-S coding for an RBM39 protein are obtained by means of a technique of quantification with amplification of nucleic acids.
12. A method as claimed in claim 1 , comprising at least the steps consisting of:
a—determining, in a biological sample isolated from said individual, before treatment with said active substance, an expression level of a long isoform of an RBM39 protein, RBM39L, and an expression level of a short isoform of an RBM39 protein, RBM39S,
b—determining a ratio of the expression levels determined in step a),
c—determining, in a biological sample isolated from said individual, after treatment with said active substance, an expression level of a long isoform of an RBM39 protein, RBM39L, and an expression level of a short isoform of an RBM39 protein, RBM39S,
d—determining a ratio of the expression levels determined in step c), and
e—comparing said ratio obtained in step d) with said ratio obtained in step b).
13. The method as claimed in claim 12 , wherein said expression levels consist respectively of (i) a transcription level of an mRNA coding for a long isoform, mRNA-L, and (ii) a transcription level of an mRNA coding for a short isoform, mRNA-S, of an RBM39 protein.
14. The method as claimed in claim 12 , wherein said expression levels consist respectively of (i) a level of production of a long isoform, ProtL, and (ii) a level of production of a short isoform, ProtS, of an RBM39 protein.
15. The method as claimed in claim 1 comprising using a kit comprising at least one pair of nucleic acid primers suitable for determining a transcription level of an mRNA coding for a long isoform, mRNA-L, and a transcription level of an mRNA coding for a short isoform, mRNA-S, of an RBM39 protein.
16. The method as claimed in claim 1 comprising using a kit comprising at least one antibody suitable for determining (i) a level of production of a long isoform, ProtL, and (ii) a level of production of a short isoform, ProtS, of an RBM39 protein.