Compositions and methods for modulating activity of capped small RNAS
Compositions and methods for modulating transcription by RNA polymerases are described.
1. An inhibitor of transcription of a target nucleic acid sequence, the inhibitor comprising a DNA nucleic acid sequence that is substantially complementary to a small priming RNA (spRNA) molecule, wherein the spRNA molecule comprises transcription initiation sequence of the target nucleic acid sequence and primes RNA transcription of the target nucleic acid sequence by an RNA polymerase, and wherein the DNA nucleic acid sequence has a sequence identity of 70% or more to the nucleotide sequence set forth in any of SEQ ID NOs: 1, 35, 36, and 37.
2. A method for inhibiting viral replication or RNA transcription by an RNA polymerase, comprising providing the inhibitor of claim 1 in an amount effective to bind to and/or inhibit the activity of the spRNA molecule.
3. The method of claim 2 , wherein said inhibiting is in a cell and said method comprises delivering the inhibitor to the cell.
4. The method of claim 2 , wherein the wherein the DNA nucleic acid sequence has a sequence identity of 70% or more to SEQ ID NO: 1.
5. The method of claim 2 , wherein the DNA nucleic acid sequence has a sequence identity of 70% or more to the sequence set forth in any of SEQ ID NOs: 35-37.
6. An inhibitor of transcription of a target nucleic acid sequence, the inhibitor comprising a polynucleotide sequence that is substantially complementary to a small priming RNA (spRNA) molecule, wherein the spRNA molecule comprises transcription initiation sequence of the target nucleic acid sequence and primes RNA transcription of the target nucleic acid sequence by an RNA polymerase,
wherein (a) the inhibitor comprises synthetic nucleic acid analogs and/or (b) the polynucleotide sequence comprised by the inhibitor is a DNA nucleic acid sequence, and wherein the target transcription initiation sequence comprises SEQ ID NO: 33 or 34.
7. The inhibitor according to claim 6 , wherein the polynucleotide sequence comprised by the inhibitor is a DNA nucleic acid sequence.
8. A method for inhibiting viral replication or RNA transcription by an RNA polymerase, comprising providing the inhibitor of claim 6 in an amount effective to bind to and/or inhibit the activity of the spRNA molecule.
9. The method of claim 8 , wherein said inhibiting is in a cell and said method comprises delivering the inhibitor to the cell.
10. The method of claim 8 , wherein the polynucleotide sequence comprised by the inhibitor is a DNA nucleic acid sequence.
11. The method of claim 10 , wherein said polynucleotide sequence comprises the sequence set forth in any of SEQ ID NOs: 35-37.
12. The inhibitor according to claim 1 , wherein the DNA nucleic acid sequence has a sequence identity of 70% or more to SEQ ID NO:1.
13. The inhibitor according to claim 1 , wherein the DNA nucleic acid sequence has a sequence identity of 80% or more to SEQ ID NO:1.
14. The inhibitor according to claim 1 , wherein the DNA nucleic acid sequence has a sequence identity of 70% or more to the sequence set forth in any of SEQ ID NOs: 35-37.
15. The inhibitor according to claim 7 , wherein said polynucleotide sequence comprises the sequence set forth in any of SEQ ID NOs: 35-37.
16. The inhibitor according to claim 7 , wherein the inhibitor comprises synthetic nucleic acid analogs.