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Sökning: L773:1097 4164

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  • Antoun, Ayman, et al. (författare)
  • How initiation factors maximize the accuracy of tRNA selection in initiation of bacterial protein synthesis
  • 2006
  • Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 23:2, s. 183-193
  • Tidskriftsartikel (refereegranskat)abstract
    • During initiation of bacterial protein synthesis, messenger RNA and fMet-tRNA(fMet) bind to the 30S ribosomal subunit together with initiation factors IF1, IF2, and IF3. Docking of the 30S preinitiation complex to the 50S ribosomal subunit results in a peptidyl-transfer competent 70S ribosome. Initiation with an elongator tRNA may lead to frameshift and an aberrant N-terminal sequence in the nascent protein. We show how the occurrence of initiation errors is minimized by (1) recognition of the formyl group by the synergistic action of IF2 and IF1, (2) uniform destabilization of the binding of all tRNAs to the 30S subunit by IF3, and (3) an optimal distance between the Shine-Dalgarno sequence and the initiator codon. We suggest why IF1 is essential for E. coli, discuss the role of the G-C base pairs in the anticodon stem of some tRNAs, and clarify gene expression changes with varying IF3 concentration in the living cell.
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  • Arab, Khelifa, et al. (författare)
  • Long Noncoding RNA TARID Directs Demethylation and Activation of the Tumor Suppressor TCF21 via GADD45A
  • 2014
  • Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 55:4, s. 604-614
  • Tidskriftsartikel (refereegranskat)abstract
    • DNA methylation is a dynamic and reversible process that governs gene expression during development and disease. Several examples of active DNA demethylation have been documented, involving genome-wide and gene-specific DNA demethylation. How demethylating enzymes are targeted to specific genomic loci remains largely unknown. We show that an antisense lncRNA, termed TARID (for TCF21 antisense RNA inducing demethylation), activates TCF21 expression by inducing promoter demethylation. TARID interacts with both the TCF21 promoter and GADD45A (growth arrest and DNA-damage-inducible, alpha), a regulator of DNA demethylation. GADD45A in turn recruits thymine-DNA glycosylase for base excision repair-mediated demethylation involving oxidation of 5-methylcytosine to 5-hydroxymethylcytosine in the TCF21 promoter by ten-eleven translocation methylcytosine dioxygenase proteins. The results reveal a function of lncRNAs, serving as a genomic address label for GADD45A-mediated demethylation of specific target genes.
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  • Bagheri, Neda, et al. (författare)
  • Commentary The new era of quantitative cell imaging-challenges and opportunities
  • 2022
  • Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 82:2, s. 241-247
  • Tidskriftsartikel (refereegranskat)abstract
    • Quantitative optical microscopy-an emerging, transformative approach to single-cell biology-has seen dramatic methodological advancements over the past few years. However, its impact has been hampered by challenges in the areas of data generation, management, and analysis. Here we outline these technical and cultural challenges and provide our perspective on the trajectory of this field, ushering in a new era of quantitative, data-driven microscopy. We also contrast it to the three decades of enormous advances in the field of genomics that have significantly enhanced the reproducibility and wider adoption of a plethora of genomic approaches.
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  • Boija, Ann, et al. (författare)
  • CBP Regulates Recruitment and Release of Promoter-Proximal RNA Polymerase II
  • 2017
  • Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 68:3, s. 491-503.e5
  • Tidskriftsartikel (refereegranskat)abstract
    • Transcription activation involves RNA polymerase II (Pol II) recruitment and release from the promoter into productive elongation, but how specific chromatin regulators control these steps is unclear. Here, we identify a novel activity of the histone acetyltransferase p300/CREB-binding protein (CBP) in regulating promoter-proximal paused Pol II. We find that Drosophila CBP inhibition results in "dribbling" of Pol II from the pause site to positions further downstream but impedes transcription through the +1 nucleosome genome-wide. Promoters strongly occupied by CBP and GAGA factor have high levels of paused Pol II, a unique chromatin signature, and are highly expressed regardless of cell type. Interestingly, CBP activity is rate limiting for Pol II recruitment to these highly paused promoters through an interaction with TFIIB but for transit into elongation by histone acetylation at other genes. Thus, CBP directly stimulates both Pol II recruitment and the ability to traverse the first nucleosome, thereby promoting transcription of most genes.
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