Roles for long noncoding RNAs (lncRNAs) in gene expression are emerging, but regulation of the lncRNA itself is poorly understood. We have identified a homeodomain protein, AtNDX, that regulates COOLAIR, a set of antisense transcripts originating from the 3' end of Arabidopsis FLOWERING LOCUS C (FLC). AtNDX associates with single-stranded DNA rather than double-stranded DNA non-sequence-specifically in vitro, and localizes to a heterochromatic region in the COOLAIR promoter in vivo. Single-stranded DNA was detected in vivo as part of an RNA-DNA hybrid, or R-loop, that covers the COOLAIR promoter. R-loop stabilization mediated by AtNDX inhibits COOLAIR transcription, which in turn modifies FLC expression. Differential stabilization of R-loops could be a general mechanism influencing gene expression in many organisms.
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http://dx.doi.org/10.1126/science.1234848 | DOI Listing |
Nat Struct Mol Biol
January 2025
Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY, USA.
Following transcript release during intrinsic termination, Escherichia coli RNA polymerase (RNAP) often remains associated with DNA in a post-termination complex (PTC). RNAPs in PTCs are removed from the DNA by the SWI2/SNF2 adenosine triphosphatase (ATPase) RapA. Here we determined PTC structures on negatively supercoiled DNA and with RapA engaged to dislodge the PTC.
View Article and Find Full Text PDFClin Transl Med
January 2025
Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
Background: Chromosomal instability (CIN), a hallmark of cancer, is commonly linked to poor prognosis in high-grade prostate cancer (PCa). Paradoxically, excessively high levels of CIN may impair cancer cell viability. Consequently, understanding how tumours adapt to CIN is critical for identifying novel therapeutic targets.
View Article and Find Full Text PDFCancer Lett
December 2024
Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang, 310058, China. Electronic address:
R-loops are critical structures that play pivotal roles in regulating genomic stability and modulating gene expression. This study investigates the interactions between the 5-methylcytosine (mC) methyltransferase NOP2/Sun RNA methyltransferase 2 (NSUN2) and R-loops in the transcriptional dynamics and damage repair process of bladder cancer (BCa) cells. We observed markedly elevated levels of R-loops in BCa cells relative to normal urothelial cells.
View Article and Find Full Text PDFFEBS Lett
December 2024
Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
Genome maintenance is essential for the integrity of the genetic blueprint, of which only a small fraction is transcribed in higher eukaryotes. DNA lesions occurring in the transcribed genome trigger transcription pausing and transcription-coupled DNA repair. There are two major transcription-coupled DNA repair pathways.
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
R-loops, RNA-DNA hybrid structures, are integral to key cellular processes such as transcriptional regulation, DNA replication, and repair. However, aberrant accumulation of R-loops can compromise genomic integrity, leading to the development of various diseases. Emerging evidence underscores the pivotal role of RNA methylation modifications, particularly N6-methyladenosine (mA) and 5-methylcytosine (mC), in orchestrating the formation, resolution, and stabilization of R-loops.
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