Human mitochondrial RNA polymerase structures reveal transcription start-site and slippage mechanism
SUMMARYHuman mitochondrial RNA polymerase (POLRMT) and protein factors TFAM and TFB2M assemble on mitochondrial DNA promoters to initiate promoter-specific transcription. We present cryo-EM structures of two initiation complexes, IC3 and slipped-IC3, with fully resolved transcription bubbles containing RNA transcripts starting from +1 and −1 positions,
Jiayu Shen +5 more
openaire +3 more sources
Strong Natural Pausing by RNA Polymerase II within 10 Bases of Transcription Start May Result in Repeated Slippage and Reextension of the Nascent RNA [PDF]
We find that immediately following transcript initiation, RNA polymerase II pauses at several locations even in the presence of relatively high (200 microM) levels of nucleoside triphosphates. Strong pauses with half-lives of >30 s were observed at +7, +18/19, and about +25 on the template used in these experiments. We show that the strong pause at +7,
Mahadeb, Pal, Donal S, Luse
openaire +2 more sources
DNA Replication Errors Drive Genome‐Wide Small Inverted Triplication Dynamics
This study provides insight into the dynamic equilibrium mechanism of a novel structural variant, small inverted triplication (SIT), which is generated by misalignment of the 3’ flap generated under DNA replication stress with palindromic sequence. Alternatively, the end sequence may fold back on itself to form an inverted fragment.
Yi Lei +12 more
wiley +1 more source
In this article, Shuai and colleagues demonstrate that metabolic remodeling drives self‐diploidization in murine haploid ESCs (haESCs). Mitochondrial dysfunction and imbalanced pyruvate metabolism underlie this process. Genome‐wide screening using haESCs identifies key mitochondrial quality‐control related genes, enabling a metabolism‐based medium that
Yi Fu +11 more
wiley +1 more source
Transcriptional errors and the drift barrier [PDF]
Population genetics predicts that the balance between natural selection and genetic drift is determined by the population size. Species with large population sizes are predicted to have properties governed mainly by selective forces; whereas species with
McCandlish, D. M., Plotkin, J. B.
core +1 more source
This study identifies S100A14 in tumor‐derived exosomes as a key driver of brain metastasis. S100A14 targets PIAS3 in astrocytes, activating STAT3 signaling and promoting immunosuppressive MDSCs recruitment via chemokine secretion. Germacrone, a natural compound, binds S100A14 to disrupt this axis, effectively inhibiting brain metastasis with low ...
Qian Feng +13 more
wiley +1 more source
Glaucoma, a major cause of blindness, involves retinal ganglion cell (RGC) degeneration. This study shows growth hormone‐releasing hormone receptor (GHRHR) deficiency preserves RGC survival and restores vision, unlike activation which only aids survival.
Yan Tong +24 more
wiley +1 more source
Transcriptional Slippage in mxiE Controls Transcription and Translation of the Downstream mxiD Gene, Which Encodes a Component of the Shigella flexneri Type III Secretion Apparatus [PDF]
ABSTRACT The Shigella flexneri transcription activator MxiE is produced by transcriptional slippage from two overlapping open reading frames. By using plasmids encoding a mxiD-lacZ translational fusion, we showed that transcriptional slippage in mxiE ...
Christophe Penno, Claude Parsot
openaire +1 more source
Stimulation of reverse transcriptase generated cDNAs with specific indels by template RNA structure: retrotransposon, dNTP balance, RT-reagent usage [PDF]
RNA dependent DNA-polymerases, reverse transcriptases, are key enzymes for retroviruses and retroelements. Their fidelity, including indel generation, is significant for their use as reagents including for deep sequencing.
Atkins, John F. +4 more
core +1 more source
This study investigates how CTCs survive varying shear stress during hematogenous metastasis. We uncover a self‐protection mechanism, by which non‐adherent CTCs adapt to high shearing milieu through accumulated cytoplasmic myosin‐mediated disruption of myosin‐actin binding, attenuating force transmission into chromatin to protect CTCs from shear ...
Cunyu Zhang +10 more
wiley +1 more source

