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Signal transduction and exercise
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Brendan Egan, Adam P. Sharples
Elongation follows the assembly of the 80S initiation complex. The process of elongation is controlled by eukaryotic elongation factors (eEFs) and uses the codons of the mRNA as a template to recruit the correct sequence of tRNA. Elongation proceeds in a cycle involving (i) binding of activated tRNA (i.e. tRNA bound with its respective amino acid), (ii) peptide bond formation and (iii) release of the inactive tRNA. The ribosome moves along the mRNA in this manner until a stop codon is reached, at which point the process is terminated by eukaryotic release factors (eRFs). Beyond the acute regulation of protein translation, the biogenesis and activity of organelles, including the ribosomes and lysosomes (autophagy, relevant to protein degradation as described later), and the importance of skeletal muscle satellite cells for adaptation (Chapter 13), are some of the emerging areas of interest in this field (10).
Familial Hyperparathyroidism
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Luigia Cinque, Alfredo Scillitani, Vito Guarnieri
The human PAF1 complex was reported to hold several functions (reviewed in [6]): It plays a role in both initiation and elongation of the transcription, associating with nonphosphorylated-Ser2 and phosphorylated-Ser5 on the C-terminal domain (CTD) of the major subunit of RNA polymerase II.In the process of transcriptional initiation, the PAF1 complex is required for the histone H2B monoubiquitination mediated by Rad6/Bre1, a prerequisite for both H3K4 and H3K79 methylation mediated by Set1 and Dot1, respectively.At initiation, the PAF1 complex associates with the Set1-like HMTase complex required for H3K4 methylation.The PAF1 complex controls elongating RNA polymerase II CTD serine 2 phosphorylation.During elongation, the PAF1 complex associates with elongation factors in conjunction with the histone chaperon FACT [79].It directly interacts with 3′-end cleavage and polyadenylation factors at an early point in the transcription cycle [77].
Translation
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
The elongation, or translocation, or stepwise addition of each aminoacyl residue to the growing polypeptide chain was the third step after the (i) codon-directed binding of the aminoacyl-tRNA to the 70S initiation complex consisting of 70S ribosome-messenger RNA-fMet-tRNAf and (ii) peptide bond formation. In addition to the ribosome-messenger RNA-aminoacyl-tRNA complex, the elongation step required GTP and three protein factors, designated as elongation factors EF-Tu, EF-Ts, and EF-G. The content and functioning of the complex were reviewed exhaustively at that time by Lucas-Lenard and Lipmann (1971) and by Haselkorn and Rothman-Denes (1973).
Preterm infants at low risk for early-onset sepsis differ in early fecal microbiome assembly
Published in Gut Microbes, 2022
Sagori Mukhopadhyay, Jung-Jin Lee, Erica Hartman, Emily Woodford, Miren B. Dhudasia, Lisa M. Mattei, Scott G. Daniel, Kelly C. Wade, Mark A. Underwood, Kyle Bittinger
To examine if the groups differed in prevalence of virulence factor-related genes, we tabulated the abundance of virulence genes from the Virulence Factors Database (VFDB) in each sample and compared the samples from the two study groups during successive time periods. Notably, we observed three genes that were more abundant among non-LRE infants, all of them differing only on days 4–7 (Figure S4). The three genes, acrB, WzzE (lipopolysaccharide biosynthesis protein), and outer membrane porin precursor, encoded structural or membrane proteins. These differences mainly tracked to the same time period where differences in microbiome composition were noted (days 4–7 of life) and the genes identified were largely absent in LRE infants. Also consistent with the dissipation of differences in microbiome composition after one week, these genes became more prevalent over time, and the abundance was not different between the study groups after day 7. We also identified 15 genes that were increased in LRE infants, including genes annotated as dnaK and elongation factor Tu (Figure 4(a) and Figure S4). The relative abundance among the 15 genes increased during the first 4 weeks after birth but we did not detect differences in the abundance of the genes after week 4. Although variants of such genes are implicated in virulence for some species, the 15 genes identified were concentrated in housekeeping and core metabolism functions.
EloA promotes HEL polyploidization upon PMA stimulation through enhanced ERK1/2 activity
Published in Platelets, 2022
Lanyue Hu, Weiwei Zhang, Zheng Xiang, Yali Wang, Cheng Zeng, Xiaojie Wang, Chengning Tan, Yichi Zhang, Fengjie Li, Yanni Xiao, Luping Zhou, Jiuxuan Li, Chun Wu, Yang Xiang, Lixin Xiang, Xiaomei Zhang, Xueying Wang, Wuchen Yang, Maoshan Chen, Qian Ran, Zhongjun Li, Li Chen
The human Elongin A (EloA) gene is located on chromosome 1p36 and encodes the transcription elongation protein EloA, which serves as the substrate recognition subunit of a CUL5/RBX2-containing Cullin-RING ubiquitin ligase that targets Pol II stalled at sites of DNA damage and perhaps other impediments [11,12]. The EloA has also been reported to act as a transcriptional activity subunit of the transcription elongation factor B (SIII) complex that stimulates the overall RNA chain synthesis rate by suppressing the frequency of transient pausing of RNA polymerase II (pol II) [13–15]. While the transcription elongation activity of EloA is related to the expression of its downstream genes, such as ATF3 and p21 [16,17], heat shock gene HSP70 [18] and retinoic acid-induced genes including Neurogenin1, Neurogenin2, NeuroD4, and Hoxa [12]. Furthermore, many biological processes have been reported to involve the EloA, such as the neuronal differentiation and development [12], early embryonic development and cellular senescence [19], and normal cell cycle progression [20]. However, the roles and molecular mechanism of EloA in MK development, especially the polyploid formation, are still unknown and require further investigations.
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
4) Shwachman Diamond Syndrome (SDS) is an autosomal recessive disease that generally manifests as bone marrow failure, skeletal deformities, and hypoplasia of the exocrine pancreas [238–240]. SBDS and GTPase elongation factor-like 1 (EFL1) directly catalyze eIF6 removal in mammalian cells via a mechanism that requires GTP binding and hydrolysis by EFL1. The SBDS protein is known to stimulate 60S dependent GTP hydrolysis by elongation factor-like 1 (EFL1), which determines the conformational change of EFL1 and eIF6 (eukaryotic initiation factor 6) removal. The dissociation of eIF6 facilitates the binding of both 40S and 60S ribosomal subunits and 80S maturation [60]. Loss of SBDS expression leads to storage of eIF6 on the late pre-60S subunit and alteration of 80S ribosome assembly [241,242].