TFOFinder: Python program for identifying purine-only double-stranded stretches in the predicted secondary structure(s) of RNA targets

Nucleic acid probes are valuable tools in biology and chemistry and are indispensable for PCR amplification of DNA, RNA quantification and visualization, and downregulation of gene expression. Recently, triplex-forming oligonucleotides (TFO) have received increased attention due to their improved se...

Celý popis

Uložené v:
Podrobná bibliografia
Vydané v:PLoS computational biology Ročník 19; číslo 8; s. e1011418
Hlavní autori: Neugroschl, Atara, Catrina, Irina E.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: San Francisco Public Library of Science 01.08.2023
Public Library of Science (PLoS)
Predmet:
Algorithms
Biology and life sciences
Catalysis
Deoxyribonucleic acid
Design
DNA
DNA probes
Double-stranded RNA
Gene expression
Genomes
Helices
Influenza
Influenza A
Inversions
Medicine and health sciences
MicroRNAs
Nucleic acids
Nucleotides
Oligonucleotides
Peptide nucleic acids
Peptides
Physical Sciences
Polyamines
Probes
Protein structure
Purines
Replication
Research and Analysis Methods
Ribonucleic acid
RNA
RNA probes
Secondary structure
Structure
Target recognition
Transcriptomes
United States
ISSN:1553-7358, 1553-734X, 1553-7358
On-line prístup:Získať plný text
Tagy: Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
Popis
Shrnutí:Nucleic acid probes are valuable tools in biology and chemistry and are indispensable for PCR amplification of DNA, RNA quantification and visualization, and downregulation of gene expression. Recently, triplex-forming oligonucleotides (TFO) have received increased attention due to their improved selectivity and sensitivity in recognizing purine-rich double-stranded RNA regions at physiological pH by incorporating backbone and base modifications. For example, triplex-forming peptide nucleic acid (PNA) oligomers have been used for imaging a structured RNA in cells and inhibiting influenza A replication. Although a handful of programs are available to identify triplex target sites (TTS) in DNA, none are available that find such regions in structured RNAs. Here, we describe TFOFinder , a Python program that facilitates the identification of intramolecular purine-only RNA duplexes that are amenable to forming parallel triple helices (pyrimidine/purine/pyrimidine) and the design of the corresponding TFO(s). We performed genome- and transcriptome-wide analyses of TTS in Drosophila melanogaster and found that only 0.3% (123) of total unique transcripts (35,642) show the potential of forming 12-purine long triplex forming sites that contain at least one guanine. Using minimization algorithms, we predicted the secondary structure(s) of these transcripts, and using TFOFinder , we found that 97 (79%) of the identified 123 transcripts are predicted to fold to form at least one TTS for parallel triple helix formation. The number of transcripts with potential purine TTS increases when the strict search conditions are relaxed by decreasing the length of the probe or by allowing up to two pyrimidine inversions or 1-nucleotide bulge in the target site. These results are encouraging for the use of modified triplex forming probes for live imaging of endogenous structured RNA targets, such as pre-miRNAs, and inhibition of target-specific translation and viral replication.
Bibliografia:new_version
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
Current address: Tri-Institutional Ph.D. Program in Chemical Biology, New York, New York, United States of America
The authors have declared that no competing interests exist.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1011418