Nejvíce citovaný článek - PubMed ID 34737002
New telomere to telomere assembly of human chromosome 8 reveals a previous underestimation of G-quadruplex forming sequences and inverted repeats
Retroviruses are among the most extensively studied viral families, both historically and in contemporary research. They are primarily investigated in the fields of viral oncogenesis, reverse transcription mechanisms, and other infection-specific aspects. These include the integration of endogenous retroviruses (ERVs) into host genomes, a process widely utilized in genetic engineering, and the ongoing search for HIV/AIDS treatment. G-quadruplexes (G4) have emerged as potential therapeutic targets in antiviral therapy and have been identified in important regulatory regions of viral genomes. In this study, we examine the presence of potential G-quadruplex-forming sequences (PQS) across all currently available unique retroviral genomes. Given that these retroviral genomes typically consist of single-stranded RNA (ssRNA) molecules, we also investigated whether the localization of PQSs is strand-dependent. This is particularly relevant since antisense transcripts have been detected in HIV, and ERV integration into the host genome involves reverse transcription from genomic positive strand ssRNA to double-stranded DNA (dsDNA), implicating both strands in this process. We show that in most mammalian retroviruses, including human retroviruses, PQSs are significantly more prevalent on the negative (antisense) strand, with some notable exceptions such as HIV-1. In sharp contrast, avian retroviruses exhibit a higher prevalence of PQSs on the positive (sense) strand.
- Klíčová slova
- Bioinformatics, G-quadruplex, G4Hunter, Persistent infection, Retroviral genome,
- MeSH
- endogenní retroviry genetika MeSH
- G-kvadruplexy * MeSH
- genom virový * MeSH
- lidé MeSH
- Retroviridae * genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Current methods of processing archaeological samples combined with advances in sequencing methods lead to disclosure of a large part of H. neanderthalensis and Denisovans genetic information. It is hardly surprising that the genome variability between modern humans, Denisovans and H. neanderthalensis is relatively limited. Genomic studies may provide insight on the metabolism of extinct human species or lineages. Detailed analysis of G-quadruplex sequences in H. neanderthalensis and Denisovans mitochondrial DNA showed us interesting features. Relatively similar patterns in mitochondrial DNA are found compared to modern humans, with one notable exception for H. neanderthalensis. An interesting difference between H. neanderthalensis and H. sapiens corresponds to a motif found in the D-loop region of mtDNA, which is responsible for mitochondrial DNA replication. This area is directly responsible for the number of mitochondria and consequently for the efficient energy metabolism of cell. H. neanderthalensis harbor a long uninterrupted run of guanines in this region, which may cause problems for replication, in contrast with H. sapiens, for which this run is generally shorter and interrupted. One may propose that the predominant H. sapiens motif provided a selective advantage for modern humans regarding mtDNA replication and function.
- Publikační typ
- časopisecké články MeSH
Cruciforms occur when inverted repeat sequences in double-stranded DNA adopt intra-strand hairpins on opposing strands. Biophysical and molecular studies of these structures confirm their characterization as four-way junctions and have demonstrated that several factors influence their stability, including overall chromatin structure and DNA supercoiling. Here, we review our understanding of processes that influence the formation and stability of cruciforms in genomes, covering the range of sequences shown to have biological significance. It is challenging to accurately sequence repetitive DNA sequences, but recent advances in sequencing methods have deepened understanding about the amounts of inverted repeats in genomes from all forms of life. We highlight that, in the majority of genomes, inverted repeats are present in higher numbers than is expected from a random occurrence. It is, therefore, becoming clear that inverted repeats play important roles in regulating many aspects of DNA metabolism, including replication, gene expression, and recombination. Cruciforms are targets for many architectural and regulatory proteins, including topoisomerases, p53, Rif1, and others. Notably, some of these proteins can induce the formation of cruciform structures when they bind to DNA. Inverted repeat sequences also influence the evolution of genomes, and growing evidence highlights their significance in several human diseases, suggesting that the inverted repeat sequences and/or DNA cruciforms could be useful therapeutic targets in some cases.
- Klíčová slova
- DNA base sequence, DNA structure, DNA supercoiling, cruciform, epigenetics, genome stability, inverted repeat, replication, transcription,
- MeSH
- DNA genetika MeSH
- konformace nukleové kyseliny MeSH
- křížová struktura DNA MeSH
- lidé MeSH
- nukleové kyseliny * MeSH
- obrácené repetice MeSH
- repetitivní sekvence nukleových kyselin genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- DNA MeSH
- křížová struktura DNA MeSH
- nukleové kyseliny * MeSH