tRNA derived small RNAs (tsRNAs) involved in cell viability
The present invention features compositions and methods relating to tRNA-derived small RNAs (tsRNAs). Provided herein are oligonucleotide compositions that are complementary to tsRNAs, in particular leuCAGtsRNA, and methods of using the oligonucleotides for the regulation of respective tsRNA. Further provided are methods of inducing apoptosis through the inhibition of leuCAGtsRNA.
1. An oligonucleotide that is complementary to a tRNA-derived small RNA (tsRNA), wherein the oligonucleotide is selected from the group consisting of:
(a) tGTcAGgAgTggGaT;
(SEQ ID NO: 2)
and
(b) GGTGtcaggagtggGATT,
(SEQ ID NO: 11)
wherein uppercase letters represent locked nucleic acids and lowercase letters represent unmodified nucleic acids.
2. A pharmaceutical composition comprising the oligonucleotide of claim 1 , and a pharmaceutically acceptable carrier.
3. A method of inhibiting viability of a cell, the method comprising administering to the cell the oligonucleotide of claim 1 .
4. The method of claim 3 , wherein the inhibiting prevents cell proliferation, induces apoptosis, or induces cellular necrosis.
5. The method of claim 4 , wherein the inhibiting induces apoptosis.
6. A method of inhibiting viability of a cell, the method comprising inhibiting the function of leucine-CAG tsRNA, said method comprising administering to said cell an amount of the oligonucleotide of claim 1 sufficient to inhibit said viability of said cell.
7. The method of claim 6 , wherein the inhibiting viability of a cell prevents cell proliferation, induces apoptosis, or induces cellular necrosis.
8. The method of claim 7 , wherein the inhibiting viability of a cell induces apoptosis.
9. The oligonucleotide of claim 1 , wherein the oligonucleotide is tGTcAGgAgTggGaT (SEQ ID NO: 2).
10. The oligonucleotide of claim 1 , wherein the oligonucleotide is GGTGtcaggagtggGATT (SEQ ID NO: 11).
11. A pharmaceutical composition comprising the oligonucleotide of claim 9 , and a pharmaceutically acceptable carrier.
12. A pharmaceutical composition comprising the oligonucleotide of claim 10 , and a pharmaceutically acceptable carrier.