Composition and methods for modulating the length of telomeres

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.

We claim:  
     
         1 . A method of modulating the length of telomeres, comprising the step of administering to a cell in vivo an amount of a molecule sufficient to modulate telomere length, wherein said molecule is: 
 a) a nucleic acid encoding hnRNP A1;    b) a nucleic acid encoding UP1;    c) a trypsin-like protease involved in the conversion of hnRNP A1 into UP1;    d) a purified hnRNP A1 polypeptide;    e) a purified UP1 polypeptide;    f) an hnRNP A1 nucleic acid molecule that is in vitro mutagenized in the portion which is absent in UP1, or a deletion, insertion, or fusion of the nucleic acid of a) or b);    g) an hnRNP A1 polypeptide that is in vitro mutagenized in the portion which is absent in UP1, or a deletion, insertion, or fusion of the molecule of any of c)-e); or    h) an agent which is specific for hnRNP A1 and/or UP1.    
     
     
         2 . The method of  claim 1 , wherein the modulation comprises the increase or stabilization of the length of telomeres.  
     
     
         3 . The method of  claim 1 , wherein the modulation comprises the decrease or destabilization of the length of telomeres.  
     
     
         4 . The method of  claim 3 , wherein said agent is an antibody having specific binding affinity to a polypeptide or epitope bearing portion of hnRNP A1 or UP1.  
     
     
         5 . The method of  claim 3 , wherein said agent is a nucleic acid complementary to the nucleic acid encoding hnRNP A1 or is a ribozyme that cleaves hnRNP A1.  
     
     
         6 . The method of  claim 5 , wherein said ribozyme is a tetrahymena-type ribozyme.  
     
     
         7 . The method of  claim 5 , wherein said ribozyme is a hammerhead-type ribozyme.  
     
     
         8 . A method for extending the ability of a cell to replicate, comprising the step of introducing in said cell in vivo an amount, sufficient to extend replication of said cell, of at least one of the following molecules: 
 a) a nucleic acid encoding hnRNP A1 or UP1;    b) a purified hnRNP A1 polypeptide, or a purified UP1 polypeptide;    c) a trypsin-like protease involved in the conversion of hnRNP A1 into UP1;    d) an hnRNP A1 nucleic acid molecule that is in vitro mutagenized in the portion which is absent in UP1, or a deletion, insertion, or fusion of the nucleic acid of a); or    e) an hnRNP A1 polypeptide that is in vitro mutagenized in the portion which is absent in UP1, or a deletion, insertion, or fusion of the molecule of b) or c).    
     
     
         9 . The method of  claim 8 , wherein wherein said introduction of a nucleic acid encoding hnRNP A1 or UP1 immortalizes said cell.  
     
     
         10 . The method of  claim 9 , wherein said nucleic acid is present in a recombinant plasmid.  
     
     
         11 . The method of  claim 9 , wherein said recombinant plasmid is an expression vector.  
     
     
         12 . The method of  claim 8 , wherein said cell is a compromised cell from a patient affected by Alzheimer's disease or Parkinson's disease.  
     
     
         13 . The method of  claim 8 , wherein said molecule is an hnRNP A1 nucleic acid that is in vitro mutagenized in the portion which is absent in UP1, or a deletion, insertion, or fusion of the nucleic acid molecule of a).  
     
     
         14 . The method of  claim 8 , wherein said molecule is an hnRNP A1 polypeptide that is in vitro mutagenized in the portion which is absent in UP1, or a deletion, insertion, or fusion of the molecule of b) or c).