De novo addition of telomeric sequences can occur at broken chromosomes and must be well controlled, which is essential during programmed DNA reorganization processes. In ciliated protozoa an extreme form of DNA-reorganization is observed during macronuclear differentiation after sexual reproduction leading to the elimination of specific parts of the germline genome. Regulating these processes involves small noncoding RNAs, but in addition DNA-reordering, excision and amplification require RNA templates deriving from the parental macronucleus. We show that these putative RNA templates can carry telomeric repeats. Microinjection of RNA templates carrying modified telomeres into the developing macronucleus leads to modified telomeres in vegetative cells, providing strong evidence, that de novo addition of telomeres depends on a telomere-containing transcript from the parental macronucleus.
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http://dx.doi.org/10.1080/15476286.2015.1134414 | DOI Listing |
Nat Commun
January 2025
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA, USA.
Biogenesis of human telomerase requires its RNA subunit (hTR) to fold into a multi-domain architecture that includes the template-pseudoknot (t/PK) and the three-way junction (CR4/5). These hTR domains bind the telomerase reverse transcriptase (hTERT) protein and are essential for telomerase activity. Here, we probe hTR structure in living cells using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) and ensemble deconvolution analysis.
View Article and Find Full Text PDFPLoS One
January 2025
Facultad de Biológicas, Instituto de Biotecnología y Biomedicina (BIOTECMED), Universitat de València, Burjassot, Spain.
The budding yeast Xrn1 protein shuttles between the nucleus, where it stimulates transcription, and the cytoplasm, where it executes the major cytoplasmic mRNA decay. In the cytoplasm, apart from catalyzing 5'→3' decay onto non translated mRNAs, Xrn1 can follow the last translating ribosome to degrade the decapped mRNA template, a process known as "cotranslational mRNA decay". We have previously observed that the import of Xrn1 to the nucleus is required for efficient cytoplasmic mRNA decay.
View Article and Find Full Text PDFBiol Lett
January 2025
Discovery, InsideOutBio , Charlestown, MA, USA.
This paper is focused on the origins of the contemporary genetic code. A novel explanation is proposed for how the mapping of nucleotides in DNA to amino acids in proteins arose that derives from repeat nucleotide sequences able to form alternative nucleic acid structures (ANS), such as the unusual left-handed Z-DNA, triplex, G-quadruplex and I-motif conformations. The scheme identifies sequence-specific contacts that map ANS repeats to dipeptide polymers (DPS).
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Ph.D. Program in Medical Neuroscience, Taipei Medical University and National Health Research Institutes, Taipei 11031, Taiwan; TMU Research Center for Drug Discovery, Taipei Medical University, Taipei 11031, Taiwan; International Master Program in Medical Neuroscience, Taipei Medical University, New Taipei City 23564, Taiwan; TMU Research Center of Neuroscience, Taipei Medical University, Taipei 11031, Taiwan; Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80780, Taiwan. Electronic address:
Traumatic brain injury (TBI) constitutes a significant burden on global healthcare systems, especially affecting younger populations, where it is a leading cause of disability and mortality. Current treatments for TBI mainly focus on preventing further brain damage and controlling symptoms. However, despite these approaches, several clinical needs remain unmet.
View Article and Find Full Text PDFbioRxiv
January 2025
Department of Biochemistry and Molecular Biology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, 52242, USA.
The human genome contains numerous repetitive nucleotide sequences that display a propensity to fold into non-canonical DNA structures including G-quadruplexes (G4s). G4s have both positive and negative impacts on various aspects of nucleic acid metabolism including DNA replication, DNA repair and RNA transcription. Poly (ADP-ribose) polymerase (PARP1), an important anticancer drug target, has been recently shown to bind a subset of G4s, and to undergo auto-PARylation.
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