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FEMS Microbiology Reviews Sep 2010Bacteria use a range of RNA regulators collectively termed small RNAs (sRNAs) to help respond to changes in the environment. Many sRNAs regulate their target mRNAs... (Review)
Review
Bacteria use a range of RNA regulators collectively termed small RNAs (sRNAs) to help respond to changes in the environment. Many sRNAs regulate their target mRNAs through limited base-pairing interactions. Ongoing characterization of base-pairing sRNAs in bacteria has started to reveal how these sRNAs participate in global regulatory networks. These networks can be broken down into smaller regulatory circuits that have characteristic behaviors and functions. In this review, we describe the specific regulatory circuits that incorporate base-pairing sRNAs and the importance of each circuit in global regulation. Because most of these circuits were originally identified as network motifs in transcriptional networks, we also discuss why sRNAs may be used over protein transcription factors to help transduce environmental signals.
Topics: Bacteria; Base Pairing; Gene Expression Regulation, Bacterial; Gene Regulatory Networks; RNA, Bacterial; RNA, Small Untranslated; Transcription Factors
PubMed: 20662934
DOI: 10.1111/j.1574-6976.2010.00241.x -
Biochimie Nov 2011Transfer-messenger RNA (tmRNA) is a bifunctional RNA that has properties of a tRNA and an mRNA. tmRNA uses these two functions to release ribosomes stalled during... (Review)
Review
Transfer-messenger RNA (tmRNA) is a bifunctional RNA that has properties of a tRNA and an mRNA. tmRNA uses these two functions to release ribosomes stalled during translation and target the nascent polypeptides for degradation. This concerted reaction, known as trans-translation, contributes to translational quality control and regulation of gene expression in bacteria. tmRNA is conserved throughout bacteria, and is one of the most abundant RNAs in the cell, suggesting that trans-translation is of fundamental importance for bacterial fitness. Mutants lacking tmRNA activity typically have severe phenotypes, including defects in viability, virulence, and responses to environmental stresses.
Topics: Bacteria; Base Pairing; Gene Expression Regulation, Bacterial; Mutation; Protein Biosynthesis; RNA, Bacterial; Ribosomes; Stress, Physiological
PubMed: 21664408
DOI: 10.1016/j.biochi.2011.05.029 -
Biochimie Nov 2023Long non-coding RNAs (lncRNAs) are recently-discovered transcripts involved in gene expression regulation and associated with diseases. Despite the unprecedented... (Review)
Review
Long non-coding RNAs (lncRNAs) are recently-discovered transcripts involved in gene expression regulation and associated with diseases. Despite the unprecedented molecular complexity of these transcripts, recent studies of the secondary and tertiary structure of lncRNAs are starting to reveal the principles of lncRNA structural organization, with important functional implications. It therefore starts to be possible to analyze lncRNA structures systematically. Here, using a set of prototypical and medically-relevant lncRNAs of known secondary structure, we specifically catalogue the distribution and structural environment of one of the first-identified and most frequently occurring non-canonical Watson-Crick interactions, the G·U base pair. We compare the properties of G·U base pairs in our set of lncRNAs to those of the G·U base pairs in other well-characterized transcripts, like rRNAs, tRNAs, ribozymes, and riboswitches. Furthermore, we discuss how G·U base pairs in these targets participate in establishing interactions with proteins or miRNAs, and how they enable lncRNA tertiary folding by forming intramolecular or metal-ion interactions. Finally, by identifying highly-G·U-enriched regions of yet unknown function in our target lncRNAs, we provide a new rationale for future experimental investigation of these motifs, which will help obtain a more comprehensive understanding of lncRNA functions and molecular mechanisms in the future.
Topics: Base Pairing; RNA, Long Noncoding; Nucleic Acid Conformation; RNA, Ribosomal; RNA, Transfer
PubMed: 37353139
DOI: 10.1016/j.biochi.2023.06.003 -
Cold Spring Harbor Perspectives in... Nov 2016In its "grand challenge" format in chemistry, "synthesis" as an activity sets out a goal that is substantially beyond current theoretical and technological capabilities.... (Review)
Review
In its "grand challenge" format in chemistry, "synthesis" as an activity sets out a goal that is substantially beyond current theoretical and technological capabilities. In pursuit of this goal, scientists are forced across uncharted territory, where they must answer unscripted questions and solve unscripted problems, creating new theories and new technologies in ways that would not be created by hypothesis-directed research. Thus, synthesis drives discovery and paradigm changes in ways that analysis cannot. Described here are the products that have arisen so far through the pursuit of one grand challenge in synthetic biology: Recreate the genetics, catalysis, evolution, and adaptation that we value in life, but using genetic and catalytic biopolymers different from those that have been delivered to us by natural history on Earth. The outcomes in technology include new diagnostic tools that have helped personalize the care of hundreds of thousands of patients worldwide. In science, the effort has generated a fundamentally different view of DNA, RNA, and how they work.
Topics: Base Pairing; DNA; Evolution, Molecular; Models, Genetic
PubMed: 27663774
DOI: 10.1101/cshperspect.a023770 -
Molecules (Basel, Switzerland) Oct 2012Strand separation is a fundamental molecular process essential for the reading of the genetic information during DNA replication, transcription and recombination.... (Review)
Review
Strand separation is a fundamental molecular process essential for the reading of the genetic information during DNA replication, transcription and recombination. However, DNA melting in physiological conditions in which the double helix is expected to be stable represents a challenging problem. Current models propose that negative supercoiling destabilizes the double helix and promotes the spontaneous, sequence-dependent DNA melting. The present review examines an alternative view and reveals how DNA compaction may trigger the sequence dependent opening of the base pairs. This analysis shows that in DNA crystals, tight DNA-DNA interactions destabilize the double helices at various degrees, from the alteration of the base-stacking to the opening of the base-pairs. The electrostatic repulsion generated by the DNA close approach of the negatively charged sugar phosphate backbones may therefore provide a potential source of the energy required for DNA melting. These observations suggest a new molecular mechanism for the initial steps of strand separation in which the coupling of the DNA tertiary and secondary interactions both actively triggers the base pair opening and stabilizes the intermediate states during the melting pathway.
Topics: Base Pairing; DNA; DNA Replication; Models, Biological; Nucleic Acid Conformation; Nucleic Acid Denaturation
PubMed: 23060287
DOI: 10.3390/molecules171011947 -
Current Protocols in Nucleic Acid... Dec 2014Base pairing in nucleic acids plays a crucial role in their structure and function. Differences in the base-pair opening and closing kinetics of individual... (Review)
Review
Base pairing in nucleic acids plays a crucial role in their structure and function. Differences in the base-pair opening and closing kinetics of individual double-stranded DNA sequences or between chemically modified base pairs provide insight into the recognition of these base pairs by DNA processing enzymes. This unit describes how to quantify the kinetics for localized base pairs by observing changes in the imino proton signals by nuclear magnetic resonance spectroscopy. The determination of all relevant parameters using state-of-the art techniques and NMR instrumentation, including cryoprobes, is discussed.
Topics: Base Pairing; DNA; Kinetics; Magnetic Resonance Spectroscopy
PubMed: 25501592
DOI: 10.1002/0471142700.nc0720s59 -
Bioinformatics (Oxford, England) Jul 2020RNA secondary structure prediction is widely used to understand RNA function. Recently, there has been a shift away from the classical minimum free energy methods to...
MOTIVATION
RNA secondary structure prediction is widely used to understand RNA function. Recently, there has been a shift away from the classical minimum free energy methods to partition function-based methods that account for folding ensembles and can therefore estimate structure and base pair probabilities. However, the classical partition function algorithm scales cubically with sequence length, and is therefore prohibitively slow for long sequences. This slowness is even more severe than cubic-time free energy minimization due to a substantially larger constant factor in runtime.
RESULTS
Inspired by the success of our recent LinearFold algorithm that predicts the approximate minimum free energy structure in linear time, we design a similar linear-time heuristic algorithm, LinearPartition, to approximate the partition function and base-pairing probabilities, which is shown to be orders of magnitude faster than Vienna RNAfold and CONTRAfold (e.g. 2.5 days versus 1.3 min on a sequence with length 32 753 nt). More interestingly, the resulting base-pairing probabilities are even better correlated with the ground-truth structures. LinearPartition also leads to a small accuracy improvement when used for downstream structure prediction on families with the longest length sequences (16S and 23S rRNAs), as well as a substantial improvement on long-distance base pairs (500+ nt apart).
AVAILABILITY AND IMPLEMENTATION
Code: http://github.com/LinearFold/LinearPartition; Server: http://linearfold.org/partition.
SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online.
Topics: Algorithms; Base Pairing; Humans; Nucleic Acid Conformation; Probability; RNA; RNA Folding; Sequence Analysis, RNA
PubMed: 32657379
DOI: 10.1093/bioinformatics/btaa460 -
PLoS Computational Biology May 2022Hoogsteen (HG) base pairing is characterized by a 180° rotation of the purine base with respect to the Watson-Crick-Franklin (WCF) motif. Recently, it has been found...
Hoogsteen (HG) base pairing is characterized by a 180° rotation of the purine base with respect to the Watson-Crick-Franklin (WCF) motif. Recently, it has been found that both conformations coexist in a dynamical equilibrium and that several biological functions require HG pairs. This relevance has motivated experimental and computational investigations of the base-pairing transition. However, a systematic simulation of sequence variations has remained out of reach. Here, we employ advanced path-based methods to perform unprecedented free-energy calculations. Our methodology enables us to study the different mechanisms of purine rotation, either remaining inside or after flipping outside of the double helix. We study seven different sequences, which are neighbor variations of a well-studied A⋅T pair in A6-DNA. We observe the known effect of A⋅T steps favoring HG stability, and find evidence of triple-hydrogen-bonded neighbors hindering the inside transition. More importantly, we identify a dominant factor: the direction of the A rotation, with the 6-ring pointing either towards the longer or shorter segment of the chain, respectively relating to a lower or higher barrier. This highlights the role of DNA's relative flexibility as a modulator of the WCF/HG dynamic equilibrium. Additionally, we provide a robust methodology for future HG proclivity studies.
Topics: Base Pairing; DNA; Hydrogen Bonding; Molecular Conformation; Nucleic Acid Conformation; Purines; Thermodynamics
PubMed: 35617357
DOI: 10.1371/journal.pcbi.1010113 -
Viruses Nov 2021The hepatitis delta virus is a single-stranded circular RNA virus, which is characterized by high self-complementarity. About 70% of the genome sequences can form...
The hepatitis delta virus is a single-stranded circular RNA virus, which is characterized by high self-complementarity. About 70% of the genome sequences can form base-pairs with internal nucleotides. There are many studies on the evolution of the hepatitis delta virus. However, the secondary structure has not been taken into account in these studies. In this study, we developed a method to examine the effect of base pairing as a constraint on the nucleotide substitutions during the evolution of the hepatitis delta virus. The method revealed that the base pairing can reduce the evolutionary rate in the non-coding region of the virus. In addition, it is suggested that the non-coding nucleotides without base pairing may be under some constraint, and that the intensity of the constraint is weaker than that by the base pairing but stronger than that on the synonymous site.
Topics: Base Pairing; Evolution, Molecular; Hepatitis D; Hepatitis Delta Virus; Humans; RNA, Viral
PubMed: 34960619
DOI: 10.3390/v13122350 -
RNA (New York, N.Y.) Apr 2015
Topics: Base Pairing; RNA
PubMed: 25780100
DOI: 10.1261/rna.050427.115