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Biomolecules Jul 2015Environmental agents are constantly challenging cells by damaging DNA, leading to the blockage of transcription elongation. How do cells deal with transcription-blockage... (Review)
Review
Environmental agents are constantly challenging cells by damaging DNA, leading to the blockage of transcription elongation. How do cells deal with transcription-blockage and how is transcription restarted after the blocking lesions are removed? Here we review the processes responsible for the removal of transcription-blocking lesions, as well as mechanisms of transcription restart. We also discuss recent data suggesting that blocked RNA polymerases may not resume transcription from the site of the lesion following its removal but, rather, are forced to start over from the beginning of genes.
Topics: Animals; DNA-Directed RNA Polymerases; Humans; RNA; Transcription Elongation, Genetic; Transcription, Genetic
PubMed: 26197343
DOI: 10.3390/biom5031600 -
Current HIV Research 2016There is a strong correlation between the use and abuse of illicit drugs and the spread of Human Immunodeficiency Virus (HIV). It is well established that illicit drugs... (Review)
Review
BACKGROUND
There is a strong correlation between the use and abuse of illicit drugs and the spread of Human Immunodeficiency Virus (HIV). It is well established that illicit drugs users are a high risk population for infection with HIV with an increased rate of HIV transmission and replication. Cocaine, amphetamine, methamphetamine, heroin and morphine stand out as the most frequently abused illicit drugs and their use correlates well with HIV infection and AIDS progression. Notably, the high incidence of HIV infection in illicit drug abusers is primarily due to high risk activities such as needle sharing and unprotected sex. Several studies have also demonstrated that drugs of abuse increase viral RNA concentrations by enhancing HIV replication, in particular in the central nervous system (CNS). The CNS is a common target for both drugs of abuse and HIV, and their synergistic action accelerates neuronal injury and cognitive impairment. In order to generate complete genomic transcripts, HIV gene expression has to progress through both the initiation and elongation phases of transcription, which requires coordinated action of different transcription factors.
CONCLUSION
In this review, we will provide the latest updates of the molecular mechanisms that regulate HIV transcription and discuss how drugs of abuse, such as cocaine, amphetamine, methamphetamine, heroin and morphine, modulate those mechanisms to upregulate HIV transcription and eventually HIV replication.
Topics: HIV; Humans; Illicit Drugs; Transcription, Genetic; Virus Replication
PubMed: 27009097
DOI: 10.2174/1570162x14666160324124736 -
Clinical and Translational Medicine Aug 2021The rapid development of technologies provides the potential to perform real-time visualization of transcriptional bursting patterns, superenhancer formation and...
The rapid development of technologies provides the potential to perform real-time visualization of transcriptional bursting patterns, superenhancer formation and sensitivity to perturbation, and interactions between enhancers, promoters, and regulators during the burst. The transcriptional bursting-induced fluctuation can modify cell capacities, cell-cell communications, cell responses to microenvironmental changes, and forms of cell death. A large number of clinical and translational studies describe the existence of heterogeneity among cells, tissues, and organs but mechanism-based understanding of how and why the heterogeneity exists and how it is formed. The transcriptional bursting, fluctuation, and control determine the development of heterogeneity and optimize cell functions in the cell development and differentiation, contribute to the initiation of cell dysfunction and tumorigenesis in response to environments, and development/evolvement of hyper/hyposensitivity to drugs. Spatiotemporal monitoring of transcriptional bursting and control provides a new insight and deeper understanding of spatiotemporal molecular medicine by integrating the transcriptional positioning and function with cell phenotypes, cell-cell communication, and clinical phenomes.
Topics: Humans; Spatio-Temporal Analysis; Transcription, Genetic; Transcriptional Activation
PubMed: 34459142
DOI: 10.1002/ctm2.518 -
Philosophical Transactions of the Royal... May 2010Spermatogenesis in mammals is achieved by multiple players that pursue a common goal of generating mature spermatozoa. The developmental processes acting on male germ... (Review)
Review
Spermatogenesis in mammals is achieved by multiple players that pursue a common goal of generating mature spermatozoa. The developmental processes acting on male germ cells that culminate in the production of the functional spermatozoa are regulated at both the transcription and post-transcriptional levels. This review addresses recent progress towards understanding such regulatory mechanisms and identifies future challenges to be addressed in this field. We focus on transcription factors, chromatin-associated factors and RNA-binding proteins necessary for spermatogenesis and/or sperm maturation. Understanding the molecular mechanisms that govern spermatogenesis has enormous implications for new contraceptive approaches and treatments for infertility.
Topics: Animals; Humans; Male; Protein Processing, Post-Translational; Spermatogenesis; Spermatozoa; Transcription, Genetic
PubMed: 20403875
DOI: 10.1098/rstb.2009.0196 -
Transcription Apr 2019The transcription cycle of RNA polymerase II (Pol II) is regulated by a set of cyclin-dependent kinases (CDKs). Cdk7, associated with the transcription initiation factor... (Review)
Review
The transcription cycle of RNA polymerase II (Pol II) is regulated by a set of cyclin-dependent kinases (CDKs). Cdk7, associated with the transcription initiation factor TFIIH, is both an effector CDK that phosphorylates Pol II and other targets within the transcriptional machinery, and a CDK-activating kinase (CAK) for at least one other essential CDK involved in transcription. Recent studies have illuminated Cdk7 functions that are executed throughout the Pol II transcription cycle, from promoter clearance and promoter-proximal pausing, to co-transcriptional chromatin modification in gene bodies, to mRNA 3ยด-end formation and termination. Cdk7 has also emerged as a target of small-molecule inhibitors that show promise in the treatment of cancer and inflammation. The challenges now are to identify the relevant targets of Cdk7 at each step of the transcription cycle, and to understand how heightened dependence on an essential CDK emerges in cancer, and might be exploited therapeutically.
Topics: Animals; Antineoplastic Agents; Cyclin-Dependent Kinases; Drug Discovery; Humans; Neoplasms; Protein Kinase Inhibitors; Transcription, Genetic; Cyclin-Dependent Kinase-Activating Kinase
PubMed: 30488763
DOI: 10.1080/21541264.2018.1553483 -
The Journal of Biological Chemistry Jul 2012DNA repair and transcription process complex nucleic acid structures. The mammalian cell can cross-utilize select components of either pathway to respond to general or... (Review)
Review
DNA repair and transcription process complex nucleic acid structures. The mammalian cell can cross-utilize select components of either pathway to respond to general or special situations arising in either path. These functions comprise activity networks capable of addressing unique requirements for each process. Here, we discuss examples of such networks that are tailored to respond to the demands of both DNA repair and transcription.
Topics: Animals; DNA; DNA Damage; DNA Repair; Gene Regulatory Networks; Humans; Models, Genetic; Transcription, Genetic
PubMed: 22605334
DOI: 10.1074/jbc.R112.377135 -
Nature Reviews. Molecular Cell Biology May 2017Transcription and chromatin function are regulated by proteins that bind to DNA, nucleosomes or RNA polymerase II, with specific non-coding RNAs (ncRNAs) functioning to... (Review)
Review
Transcription and chromatin function are regulated by proteins that bind to DNA, nucleosomes or RNA polymerase II, with specific non-coding RNAs (ncRNAs) functioning to modulate their recruitment or activity. Unlike ncRNAs, nascent pre-mRNA was considered to be primarily a passive player in these processes. In this Opinion article, we describe recently identified interactions between nascent pre-mRNAs and regulatory proteins, highlight commonalities between the functions of nascent pre-mRNA and nascent ncRNA, and propose that both types of RNA have an active role in transcription and chromatin regulation.
Topics: Animals; Cell Nucleus; Chromatin; Gene Expression Regulation; Humans; RNA Splicing; Repressor Proteins; Transcription Elongation, Genetic; Transcription Factors; Transcription, Genetic
PubMed: 28270684
DOI: 10.1038/nrm.2017.12 -
The Journal of Biological Chemistry Sep 2021Transcriptional regulation is one of the key steps in determining gene expression. Diverse single-molecule techniques have been applied to characterize the stepwise... (Review)
Review
Transcriptional regulation is one of the key steps in determining gene expression. Diverse single-molecule techniques have been applied to characterize the stepwise progression of transcription, yielding complementary results. These techniques include, but are not limited to, fluorescence-based microscopy with single or multiple colors, force measuring and manipulating microscopy using magnetic field or light, and atomic force microscopy. Here, we summarize and evaluate these current methodologies in studying and resolving individual steps in the transcription reaction, which encompasses RNA polymerase binding, initiation, elongation, mRNA production, and termination. We also describe the advantages and disadvantages of each method for studying transcription.
Topics: DNA; DNA-Directed RNA Polymerases; Fluorescence Resonance Energy Transfer; Gene Expression; Gene Expression Regulation; Microscopy, Atomic Force; Microscopy, Fluorescence; Protein Binding; Single Molecule Imaging; Transcription, Genetic
PubMed: 34403697
DOI: 10.1016/j.jbc.2021.101086 -
Journal of Applied Physiology... Aug 2019Skeletal muscle mass responds in a remarkable manner to alterations in loading and use. It has long been clear that skeletal muscle hypertrophy can be prevented by... (Review)
Review
Skeletal muscle mass responds in a remarkable manner to alterations in loading and use. It has long been clear that skeletal muscle hypertrophy can be prevented by inhibiting RNA synthesis. Since 80% of the cell's total RNA has been estimated to be rRNA, this finding indicates that de novo production of rRNA via transcription of the corresponding genes is important for such hypertrophy to occur. Transcription of rDNA by RNA Pol I is the rate-limiting step in ribosome biogenesis, indicating in turn that this biogenesis strongly influences the hypertrophic response. The present minireview focuses on ) a brief description of the key steps in ribosome biogenesis and the relationship of this process to skeletal muscle mass and ) the coordination of ribosome biogenesis and protein synthesis for growth or atrophy, as exemplified by the intracellular AMPK and mTOR pathways.
Topics: Animals; Humans; Hypertrophy; Muscle, Skeletal; Muscular Diseases; Protein Biosynthesis; RNA, Ribosomal; Ribosomes; Transcription, Genetic
PubMed: 31219775
DOI: 10.1152/japplphysiol.00963.2018 -
Experientia Supplementum (2012) 2014The DNA-dependent RNA polymerases induce specific conformational changes in the promoter DNA during transcription initiation. Fluorescence spectroscopy sensitively... (Review)
Review
The DNA-dependent RNA polymerases induce specific conformational changes in the promoter DNA during transcription initiation. Fluorescence spectroscopy sensitively monitors these DNA conformational changes in real time and at equilibrium providing powerful ways to estimate interactions in transcriptional complexes and to assess how transcription is regulated by the promoter DNA sequence, transcription factors, and small ligands. Ensemble fluorescence methods described here probe the individual steps of promoter binding, bending, opening, and transition into the elongation using T7 phage and mitochondrial transcriptional systems as examples.
Topics: Animals; Binding Sites; DNA; DNA-Directed RNA Polymerases; Fluorescent Dyes; Humans; Kinetics; Molecular Probe Techniques; Nucleic Acid Conformation; Optical Imaging; Promoter Regions, Genetic; Spectrometry, Fluorescence; Transcription Elongation, Genetic; Transcription Initiation, Genetic; Transcription, Genetic
PubMed: 25095993
DOI: 10.1007/978-3-0348-0856-9_6