Rna products and uses thereof

Abstract

Small RNAs, inhibitors thereof, inhibitors of enzymes producing small RNAs, and the use of these to modulate the response of a cell to a DNA damaging event. A method of detecting the presence of, or of quantifying DNA damage.

1 . A method of detecting damage to DNA in a sequence-specific genomic locus in a cell comprising:
 detecting the presence of small RNAs (DDRNAs), said small RNAs being generated by processing by DICER and/or DROSHA of a RNA transcript synthesized upon transcription of the damaged genomic locus in said cell; and   comparing the result to a control cell with undamaged DNA genomic locus.   
     
     
         2 . A method of identifying the genomic location of damage to DNA in a sequence-specific genomic locus in a cell comprising:
 isolating and/or purifying small RNAs (DDRNAs) from a sample, said small RNAs being generated by processing by DICER and/or DROSHA of a RNA transcript synthesized upon transcription of the damaged genomic locus in said cell; and   sequencing said isolated and/or purified small RNAs (DDRNAs).   
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein detecting the presence of the DDRNAs comprises measuring an amount of the DDRNAs; and
 comparing the result to a proper control,   wherein the comparison to the proper control allows diagnosing and/or prognosing a condition associated with and/or induced by generation of DNA damage in at least one sequence specific genomic locus.   
     
     
         5 . The method according to  claim 4 , wherein the condition associated with and/or induced by the generation of DNA damage in at least one sequence specific genomic locus is selected from the group consisting of: cancer, aging and viral infection. 
     
     
         6 . The method according to  claim 5  wherein aging is associated with critically short and/or damaged and/or dysfunctional telomeres. 
     
     
         7 . The method of  claim 4 , further comprising:
 after administration of a therapy for a condition associated with and/or induced by the generation of DNA damage in at least one sequence specific genomic locus, measuring an amount of the DDRNAs; and   comparing the result to a proper control,   wherein the comparison to the proper control allows for monitoring efficacy of the therapy.   
     
     
         8 . The method according to  claim 7  wherein the condition associated with and/or induced by the generation of DNA damage in at least one sequence specific genomic locus is selected from the group consisting of: cancer, aging and viral infection. 
     
     
         9 . The method according to  claim 8  wherein aging is associated with damaged telomeres. 
     
     
         10 . A method of screening for an agent able to inhibit small RNAs (DDRNAs), said small RNAs being generated by processing by DICER and/or DROSHA of a RNA transcript synthesized upon transcription of a damaged genomic locus in a cell comprising measuring an amount of said small RNAs upon exposure of the cell to said agent, and comparing to a proper control. 
     
     
         11 . The method of  claim 1 , wherein the cell is a mammalian cell. 
     
     
         12 . The method of  claim 11 , wherein the mammalian cell is a human cell. 
     
     
         13 . The method of  claim 12 , wherein the cell is selected from the group consisting of a pre-cancerous, cell, a cancer cell, a senescent cell and a viral cell. 
     
     
         14 . The method of  claim 13 , wherein the senescent cell has critically short and/or damaged and/or dysfunctional telomeres. 
     
     
         15 . The method of  claim 2 , wherein the cell is a human cell. 
     
     
         16 . The method of  claim 15 , wherein the cell is selected from the group consisting of a pre-cancerous, cell, a cancer cell, a senescent cell and a viral cell. 
     
     
         17 . The method of  claim 16 , wherein the senescent cell has critically short and/or damaged and/or dysfunctional telomeres. 
     
     
         18 . The method of  claim 10 , wherein the cell is a human cell. 
     
     
         19 . The method of  claim 18 , wherein the cell is selected from the group consisting of a pre-cancerous, cell, a cancer cell, a senescent cell and a viral cell. 
     
     
         20 . The method of  claim 19 , wherein the senescent cell has critically short and/or damaged and/or dysfunctional telomeres.