Polycomb-associated Non-Coding RNAs

Abstract

This invention relates to long non-coding RNAs (lncRNAs), libraries of those lncRNAs that bind chromatin modifiers, such as Polycomb Repressive Complex 2, inhibitory nucleic acids and methods and compositions for targeting lncRNAs.

1 . An inhibitory nucleic acid that specifically binds, or is complementary to, an RNA that is known to bind to Polycomb repressive complex 2 (PRC2), optionally an RNA of SEQ ID NO: 17040, or an RNA of any of Tables 1-8 or an RNA of any of SEQ ID NOs: 1 to 193,049, for use in the treatment of disease, wherein the treatment involves modulating expression of a gene targeted by the RNA, wherein the inhibitory nucleic acid is between 5 and 40 bases in length, and wherein the inhibitory nucleic acid is formulated as a sterile composition. 
     
     
         2 . A process of preparing the inhibitory nucleic acid of  claim 1  that binds an RNA that binds to Polycomb repressive complex 2 (PRC2), the process comprising the step of designing and/or synthesizing a nucleic acid of between 5 and 40 bases in length, wherein the RNA is SEQ ID NO: 17040, or an RNA of any of Tables 1-8 or an RNA of any of SEQ ID NOS: 1 to 193,049, wherein the inhibitory nucleic acid is complementary to at least . 
     
     
         3 . A method of increasing gene expression of a target gene comprising administering to a mammal the inhibitory nucleic acid of  claim 1 , in an amount effective to increase expression of the gene targeted by the RNA. 
     
     
         4 . The method of  claim 2 , wherein the target gene is an oncogene or tumor suppressor, and the inhibitory nucleic acid specifically binds, or is complementary to, an RNA of Table 6 or Table 7. 
     
     
         5 . A method of inhibiting or suppressing tumor growth in a mammal in need thereof comprising administering to said mammal an inhibitory nucleic acid that binds, or is complementary to a human RNA sequence corresponding to a mouse RNA sequence of any of SEQ ID NOs: 1 to 49, or 12,268 to 12,603 in an amount effective to suppress or inhibit tumor growth. 
     
     
         6 . A method of decreasing expression of an oncogene in a cell, the method comprising contacting the cell with a mouse RNA sequence of any one of SEQ ID NOS: 12,053 to 12,267 or a corresponding human RNA sequence optionally having a nucleobase sequence of any one of SEQ ID NOS: 21,195 to 21,337, or 192,980 to 193,006, or a fragment thereof at least 20 bases in length that retains PRC2-binding activity.