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Methods in molecular exercise physiology
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Adam P. Sharples, Daniel C. Turner, Stephen Roth, Robert A. Seaborne, Brendan Egan, Mark Viggars, Jonathan C. Jarvis, Daniel J. Owens, Jatin G. Burniston, Piotr P. Gorski, Claire E. Stewart
Gene transcription is first initiated by the protein, RNA polymerase, that binds to a transcription factor complex located within the ‘promoter’ region of the gene on the DNA. This process begins at the transcription initiation site where RNA polymerase begins transcribing the corresponding single-stranded RNA (ssRNA) encoded by the targeted dsDNA sequence in the 5’ to 3’ (or left to right) direction. The resultant pre-mRNA molecule then undergoes several post-transcriptional modifications to remove or ‘splice’ the non-coding regions (i.e. introns) of the mRNA. Therefore, the final mature mRNA product only contains the coding regions of the gene (i.e. exons) ready to be subsequently translated into protein by the ribosomes in the cytoplasm (Chapter 3, Figures 3.8 and 3.9). Many copies of RNA can then be produced from one gene. It is often the amount of mature mRNA that researchers will want to measure due to its protein coding potential. To analyse whether an exercise intervention has increased or decreased gene transcription levels of individual genes, RNA must be first isolated, quantified and checked for its ‘quality’ as described earlier in this chapter. Finally, RNA can then be analysed via a method called reverse transcription real-time quantitative polymerase chain reaction (rt-RT-qPCR).
Introduction to Genomics
Published in Altuna Akalin, Computational Genomics with R, 2020
In summary, the set of processes, from transcription initiation to production of the functional product, is referred to as gene expression. Gene expression quantification and regulation is a fundamental topic in genome biology.
Genetics of immunoglobulins: Ontogenic, biological, and clinical implications
Published in Gabriel Virella, Medical Immunology, 2019
The transcription of Ig genes, like other eukaryotic genes, is regulated by promoters and enhancers. Promoters, located 5′ of the V segments, are necessary for transcription initiation. Enhancers, located in the introns between J and C segments, increase the rate of transcription. For this reason, immunoglobulin synthesis (H or L chains) is only detected after the VDJ or VJ rearrangements, which bring the promoter in close proximity to the enhancer.
Transcriptomic analysis of the Non-Obstructive Azoospermia (NOA) to address gene expression regulation in human testis
Published in Systems Biology in Reproductive Medicine, 2023
Govindkumar Balagannavar, Kavyashree Basavaraju, Akhilesh Kumar Bajpai, Sravanthi Davuluri, Shruthi Kannan, Vasan S. Srini, Darshan S. Chandrashekar, Neelima Chitturi, Kshitish K. Acharya
About 61 and 42% of Td250 and Td3000 transcripts, respectively, were the principal transcript isoforms. Similarly, about 51 and 37% of the up-regulated transcripts were the principal isoforms among the Tu250 and Tu3000, respectively. Only 8 of the Tu250 and 9 of the Td250genes, respectively, had a completely opposing expression among their iso-mRNAs. The transcript ENST00000618113 of the down-regulated SPAG9 gene was one such example. The cases of partial contradictions (i.e., up-/down-regulation vs. non-differentiated transcripts from a gene) were more, with 121 and 43 cases among the Tu250 and Td250 genes, respectively. The regions with functional domains did not seem to be altered across the transcript isoforms of most genes. However, the transcription initiation and termination sites were altered in many cases. This observation indicates a potential change in the NOA-associated gene expression regulation mechanisms, mainly at the transcription initiation and post-transcriptional phases involving promoters and the 5' and 3' UTRs.
Convergent neurobiological predictors of mood and anxiety symptoms and treatment response
Published in Expert Review of Neurotherapeutics, 2019
Mbemba Jabbi, Charles B. Nemeroff
The general transcription factor 2I (GTF2i) gene is implicated in RNA polymerase II transcription initiation, promotor clearance, and translational control [23]. GTF2i is a transcriptional co-activator with the functional ability to bind to promotor elements of many genes [23]. CNVs of GTF2i [24] and sequence variations [25] have been implicated in anxiety phenotypes [24]. Hemizygosity for transcriptional activators and related DNA-binding proteins have functionally relevant dose-sensitive effects on social and anxiety phenotypes in human multi-system disorders such as the chromosome 7q11.23 hemideletion that causes Williams syndrome (WS) [26]. Remarkably, this genetic CNV is marked by over 70% prevalence of anxiety and abnormal insular pathway structure and function [26,27].
Ribosomopathies and cancer: pharmacological implications
Published in Expert Review of Clinical Pharmacology, 2022
Gazmend Temaj, Sarmistha Saha, Shpend Dragusha, Valon Ejupi, Brigitta Buttari, Elisabetta Profumo, Lule Beqa, Luciano Saso
The preinitiation complex consists of upstream binding factors (UBF), a selective factor (SL1, known as TIF1-B), transcription initiation factor 1A (TIF1A), and Pol I. UBF marks the promoter region by binding to the core promoter that surrounds the transcription start site. SL1 is then recruited to the promoter and directs promoter-specific transcription initiation. Functional interactions among UBF, SL1, and the human rRNA promoter are fundamental for promoter function and rRNA synthesis. Recruitment of the TATA-binding protein-TAFI complex SL1 to human ribosomal DNA promoters is mediated by the carboxyl-terminal activation domain of UBF, which is regulated by UBF phosphorylation [34]. TIF-1A interacts with Pol-I, which is essential for PIC formation [35,36].