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Connective tissue disease
Published in Catherine Nelson-Piercy, Handbook of Obstetric Medicine, 2020
There may be associated anti-nuclear, anti-centromere (associated with limited cutaneous systemic sclerosis/CREST syndrome), anti-nucleolar or topoisomerase I (Scl-70) antibodies (associated with diffuse cutaneous scleroderma and lung involvement). RNA-polymerase III antibodies are a marker of rapid aggressive onset disease and are associated with pulmonary hypertension, but this may also develop secondary to lung disease.
Mobile DNA Sequences and Their Possible Role in Evolution
Published in S. K. Dutta, DNA Systematics, 2019
Georgii P. Georgiev, Yurii V. Ilyin, Alexei P. Ryskov, Tatiana I. Gerasimova
An important common feature of these sequences is the presence of the regions reminiscent of the split RNA polymerase III promoter. The consensus sequence for the latter is deduced from the analysis of several RNA-polymerase III genes.118–125 The location of a possible promoter within short repeats is such that the transcription should start from the beginning of the sequence.126–128 At the opposite end, the short repeats contain an A-rich region. In addition, B2 contains the signals for RNA-polymerase III termination and several polyadenylation signals, AATAAA.31
Introduction to Molecular Biology
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Unlike prokaryote, eukaryotes require transcription factors to initiate transcription process. The transcription factors must bind the promoter region in DNA and form an appropriate initiation complex before the initiation of the transcription. In eukaryotic cells, three types of RNA polymerases (RNA polymerase I, II, and III) are involved in this process. The promoter region is constituted of specific nucleic acid sequence recognized by the polymerase. There are various types of promoters, such as the TATA box or the CATT box promoter regions, but all of them contain the specific sequence referred to as the starting site of transcription. In the vast majority of eukaryotic genes, the RNA polymerase II is responsible of the initiation of transcription. For the correct initiation of the transcription, the transcription factors must interact with the promoter region in a specific order. For example, in order to bind to the promoter region and initiate transcription efficiently, the DNA polymerase II (Fig. 10) requires transcription factors: TFIID, TFIIA, TFIIB, TFIIF, and TFIIE (Transcription Factor for Polymerase II). After the arrival of the transcription factors, the polymerase II can bind to the promoter region and begin the transcription. Usually, the promoters for the genes transcribed by the RNA polymerases are situated upstream from the transcription start points, with some exceptions such as the genes transcribed by the RNA polymerase III.
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
Ribosome biogenesis begins with rRNA synthesis in the nucleolus, and the first step involves the formation of a preinitiation complex (PIC) around the rDNA promoter region. During ribosome biogenesis, RNA polymerase I (Pol I) is shown to transcribe rRNA genes into a single polycistronic transcript that is cleaved into 18S, 5.8S, and 28S rRNAs. During processing, many small nucleolar ribonucleoparticles (snoRNP) facilitate the modification of numerous rRNA residues [29,30], such as pseudouridylation and methylation (M), which plays pivotal roles in ribosomal maturation. These RNA transcripts in 5’ site form the 90S ‘processome’ complex. This complex 90S was cleaved to form pre-40S and 60S particles. In the nucleoplasm, RNA polymerase II (Pol II) and RNA polymerase III (Pol III) are involved in the transcription of the ribosomal protein (RPs) and 5S rRNA genes [31]. (Figure 1). Ribosomal proteins (RPs) after that are shown to stabilize small and large subunits, rRNA processing, pre-ribosome transport, RNA folding, and interaction of other factors that are required for ribosome synthesis or translation [32]. The RNA splicing process is very complex and has been described by many authors (see reviews by Watkins and Bohnsack [33], Lafontaine [290], and Rahhal and Seto [291].
Current progress of miRNA-derivative nucleotide drugs: modifications, delivery systems, applications
Published in Expert Opinion on Drug Delivery, 2022
Charles Asakiya, Liye Zhu, Jieyu Yuhan, Longjiao Zhu, Kunlun Huang, Wentao Xu
The biogenesis of miRNAs begins with the post- or co-transcriptional processing of RNA polymerase/III transcripts[8]. In the canonical pathway, Drosha (a Class 2 ribonuclease III enzyme) and DiGeorge syndrome critical region 8 (DGCR8) enzymes break the primary miRNA (pri-miRNA) into the precursor miRNA (pre-miRNA) in the first step. The pre-miRNA is also cut by Dicer to make double-stranded RNAs, which are then linked to Argonaute (AGO) proteins to make the RNA-induced silencing complex (RISC). Exportin 5 then moves the pre-miRNA into the cytoplasm. There is evidence for miRNA-coding sequence and gene promoter interactions. The mechanism of miRNA’s attachment to the 5′ untranslated region (UTR) and coding areas to silence gene expression and the functional relevance of these interactions has also been reported. miRNAs can also be transported between cells to regulate translation and transcription. Recent research shows miRNA-mediated gene regulation is complex, and the disruption of miRNA activity is linked with disease onset and progression. The pool of possible targets is limited due to cell type-specific gene expression and compartmentalization.
The role of mTOR in age-related diseases
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Zofia Chrienova, Eugenie Nepovimova, Kamil Kuca
In addition, the synthesis of rRNAs and tRNAs is positively controlled by mTORC1. Mammalian RNA Polymerase I (Pol I) transcribes precursor rRNA that sequentially forms three out of four mature rRNA species (5.8S, 18S, and 28S), while RNA Polymerase III (Pol III) transcribes the fourth RNA species, 5S rRNA, as well as tRNA. Pol I can be activated by the mTORC1 effector S6K1 or by the mTORC1-mediated phosphorylation of transcription initiation factor IA (TIF1A), which is then translocated to the nucleolus, where it can activate Pol I44,45. mTORC1 also phosphorylates (and consequently inhibits) the repressor of RNA polymerase III transcription MAF1 homolog (MAF1)46. Moreover, the direct binding of mTORC1 to the promoter region of Pol I and Pol III increases gene expression47.