Transcription-mediated binding of peptide nucleic acid (PNA) to double-stranded DNA: sequence-specific suicide transcription

TY - JOUR

T1 - Transcription-mediated binding of peptide nucleic acid (PNA) to double-stranded DNA

T2 - sequence-specific suicide transcription

AU - Larsen, H J

AU - Nielsen, Peter E.

PY - 1996/2/1

Y1 - 1996/2/1

N2 - Peptide nucleic acid (PNA) forms sequence-specific (PNA)2/DNA triplexes with one strand of double-stranded DNA by strand invasion. When formed with the template strand of DNA such a (PNA)2/DNA triplex can arrest transcription elongation in vitro and can thus act as an anti-gene agent. One of the major obstacles to applying PNA as an anti-gene agent in vivo is that PNA strand invasion occurs at a very slow rate under moderate salt conditions. In the present study we show that transcription can increase the rate of sequence-specific PNA binding dramatically. Such transcription-mediated PNA binding occurs three times as efficiently when the PNA target is situated on the non- template strand as compared with the template strand. Since transcription can mediate template strand-associated (PNA)2/DNA complexes which arrest further elongation, the action of RNA polymerase results in repression of its own activity, i.e. suicide transcription. These findings are highly relevant for the possible future use of PNA as an anti-gene agent.

AB - Peptide nucleic acid (PNA) forms sequence-specific (PNA)2/DNA triplexes with one strand of double-stranded DNA by strand invasion. When formed with the template strand of DNA such a (PNA)2/DNA triplex can arrest transcription elongation in vitro and can thus act as an anti-gene agent. One of the major obstacles to applying PNA as an anti-gene agent in vivo is that PNA strand invasion occurs at a very slow rate under moderate salt conditions. In the present study we show that transcription can increase the rate of sequence-specific PNA binding dramatically. Such transcription-mediated PNA binding occurs three times as efficiently when the PNA target is situated on the non- template strand as compared with the template strand. Since transcription can mediate template strand-associated (PNA)2/DNA complexes which arrest further elongation, the action of RNA polymerase results in repression of its own activity, i.e. suicide transcription. These findings are highly relevant for the possible future use of PNA as an anti-gene agent.

KW - Base Sequence

KW - DNA/genetics

KW - Molecular Sequence Data

KW - Oligonucleotides/genetics

KW - Sequence Analysis

KW - Templates, Genetic

KW - Transcription, Genetic

M3 - Journal article

C2 - 8602358

SN - 0305-1048

VL - 24

SP - 458

EP - 463

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 3

ER -