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The DNA of all living organisms is a common matrix for both replication and transcription processes. This sometimes leads to inevitable collisions between DNA replication and transcription machinery. There is plethora of evidence demonstrating that such collisions (or TRCs) are one of the most common and significant reasons for genomic instability. One of the key outcomes of TRCs is the accumulation of non-canonical DNA secondary structures, including R-loops. R-loops are three-stranded DNA-RNA hybrids with a displaced third single-stranded DNA fragment. Although R-loops are thought to play several functional roles in biological processes, an imbalance in their metabolism has been proven to have severe consequences. In this review, we attempt to summarize the current knowledge of the participants in the process of R-loop regulation in cells, with an emphasis on eukaryotic systems. We also touch upon the conditions favoring TRCs and the possible ways of dealing with these conflicts.
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http://dx.doi.org/10.3390/ijms26146951 | DOI Listing |
Hum Genet
September 2025
College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, 28 Fuxing Road, Beijing, 100853, China.
Recessive variants in TWNK cause syndromes arising from mitochondrial DNA (mtDNA) depletion. Hearing loss is the most prevalent manifestation in individuals with these disorders. However, the clinical and pathophysiological features have not been fully elucidated.
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September 2025
Faculty of Medicine in Pilsen, Biomedical Center, Charles University, Prague, Czech Republic.
Mitochondria in the egg are suggested to be crucial for the onset of new life. However, there is ambiguous knowledge about the necessity for fertilization and early embryonic development. Therefore, we created a conditional Tfam knockout (Tfam; Zp3-Cre) to produce Tfam oocytes for investigation of the mitochondrial abundance in oocytes and early embryos.
View Article and Find Full Text PDFCell Signal
September 2025
Departments of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address:
Mature mRNAs are generated by spliceosomes that recruit factors to aid RNA splicing in which introns are removed and exons joined. Among the splicing factors, a family of proteins contain a homologous U2 Auxiliary Factor (U2AF) Homology Motif (UHM) to bind with factors containing U2AF ligand motifs (ULM) and recruit them to regulate 3' splice site selection. Mutations and overexpression of UHM splicing factors are frequently found in cancers.
View Article and Find Full Text PDFJ Mol Biol
September 2025
University of South Alabama, Department of Physiology and Cell Biology, 5851 USA Dr. North, Mobile, AL 36688, USA. Electronic address:
In sexually reproducing eukaryotes-particularly mammals-mitochondrial DNA (mtDNA) is typically inherited from a single parent, making uniparental mtDNA inheritance a fundamental feature of eukaryotic biology. Recently, it has been suggested that spermatozoa contain no mtDNA because the matrix targeting sequence (MTS) of the mitochondrial transcription factor A (TFAM) becomes phosphorylated, which prevents the mitochondrial import of this protein essential for mtDNA replication. In this study, we used a combination of the GeneSwap technique and phosphomimetic mutations to investigate the impact of TFAM MTS phosphorylation on mtDNA maintenance in cultured cells.
View Article and Find Full Text PDFBlood Adv
September 2025
Institut de Recherches Cliniques de Montreal - IRCM, Montreal, Quebec, Canada.
Acute myeloid leukemia (AML) with rearrangement of the mixed lineage leukemia gene express MLL-AF9 fusion protein, a transcription factor that impairs differentiation and drives expansion of leukemic cells. We report here that the zinc finger protein GFI1 together with the histone methyltransferase LSD1 occupies the promoter and regulates expression of the lncRNA ELDR in the MLL-r AML cell line THP-1. Forced ELDR overexpression enhanced the growth inhibition of an LSD1i/ATRA combination treatment and reduced the capacity of these cells to generate leukemia in xenografts, leading to a longer leukemia-free survival.
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