We identified 29 G-quadruplex binding proteins by affinity purification and quantitative LC-MS/MS. We demonstrated that the DEAD-box RNA helicases Dbp2, Ded1 and Mss116 preferentially bind to G-quadruplex nucleic acids in vitro and destabilize RNA quadruplexes, suggesting new potential roles for these helicases in disruption of quadruplex structures in RNA.
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http://dx.doi.org/10.1039/c8cc10091h | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, TX 75080.
The TRAMP complex contains two enzymatic activities essential for RNA processing upstream of the nuclear exosome. Within TRAMP, RNA is 3' polyadenylated by a subcomplex of Trf4/5 and Air1/2 and unwound 3' to 5' by Mtr4, a DExH helicase. The molecular mechanisms of TRAMP assembly and RNA shuffling between the two TRAMP catalytic sites are poorly understood.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Laboratory of Obesity and Aging Research, Cardiovascular Branch, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892.
Mitochondrial endonuclease G (EndoG) contributes to chromosomal degradation when it is released from mitochondria during apoptosis. It is presumed to also have a mitochondrial function because EndoG deficiency causes mitochondrial dysfunction. However, the mechanism by which EndoG regulates mitochondrial function is not known.
View Article and Find Full Text PDFGenetics
December 2024
Department of Life Science and Biotechnology, Jadavpur University, Kolkata 7000 32, India.
In Saccharomyces cerevisiae, SKS1 mRNA encoding a glucose-sensing serine/threonine kinase belongs to "nucleus-retained" (NR) mRNAs representing a subset of otherwise normal transcripts, which exhibits slow nuclear export and excessively long nuclear dwell time. Nuclear retention of the SKS1 mRNA triggered by a 202 nt "export-retarding" nuclear zip code (NZ) element promotes its rapid degradation in the nucleus by the nuclear exosome/CTEXT. In this investigation, we demonstrate that Dbp2p, an ATP-dependent DEAD-box RNA helicase binds to SKS1 and other NR-mRNAs and thereby inhibits their export by antagonizing with the binding of the export factors Mex67p/Yra1p.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia University Irving Medical Center, New York, NY, USA.
Pluripotent stem cells possess a unique nuclear architecture characterized by a larger nucleus and more open chromatin, which underpins their ability to self-renew and differentiate. Here, we show that the nucleolus-specific RNA helicase DDX18 is essential for maintaining the pluripotency of human embryonic stem cells. Using techniques such as Hi-C, DNA/RNA-FISH, and biomolecular condensate analysis, we demonstrate that DDX18 regulates nucleolus phase separation and nuclear organization by interacting with NPM1 in the granular nucleolar component, driven by specific nucleolar RNAs.
View Article and Find Full Text PDFMol Cell
December 2024
Biotechnology Center, Center for Molecular and Cellular Bioengineering, TU Dresden, Dresden 01307 Saxony, Germany; Cluster of Excellence Physics of Life, TU Dresden, Dresden 01307 Saxony, Germany. Electronic address:
Ribonucleoprotein (RNP) granules have been linked to translation regulation and disease, but their assembly and regulatory mechanisms are not well understood. Here, we show that the RNA-binding protein G3BP1 preferentially interacts with unfolded RNA, driving the assembly of RNP granule-like condensates that establish RNA-RNA interactions. These RNA-RNA interactions limit the mobility and translatability of sequestered mRNAs and stabilize the condensates.
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