Translation
Paul Pumpens in Single-Stranded RNA Phages, 2020
Olsthoorn et al. (1995b) demonstrated coevolution of the RNA helix stability and SD complementarity in the MS2 coat translational start region. Thus, the changes were made in the SD that shortened or extended its complementarity to the 3′ end of 16S rRNA, and their evolution to a stable pseudorevertant species was monitored in vivo in live MS2 phage. The results showed that the phages in which the SD complementarity was decreased evolved an initiator hairpin of lower stability than wild-type, while those in which the complementarity was extended evolved a hairpin with increased stability. It was concluded that weaker SD sequences still allowed maximal translation if the secondary structure of the ribosome-landing site was destabilized accordingly. Alternatively, translation-initiation regions with a stronger secondary structure still allowed maximal expression if the SD complementarity was extended. These findings supported the idea that the SD interaction helped the ribosome to melt the structure in the translation-initiation region (Olsthoorn et al. 1995b).
Signal transduction and exercise
Adam P. Sharples, James P. Morton, Henning Wackerhage in Molecular Exercise Physiology, 2022
While all three processes are tightly regulated, the rate-limiting step for translational control occurs at the initiation step. Translation initiation is a multi-step process regulated by eukaryotic initiation factors (eIFs) and culminates in formation of the 80S initiation complex. Prior to translation, the subunits of the ribosome are separate and the 40S subunit must be ‘primed’ by binding of a transfer RNA (tRNA). The tRNA contains the complementary sequence for the AUG start codon of mRNA and is also attached to the amino acid methionine. Proteins are synthesised beginning from the amine N-terminal and ending with a carboxyl C-terminal; therefore, all proteins begin with a methionine residue, although this is often removed after translation. The priming of the 40S ribosome is regulated in part by eIF3 and creates a 43S pre-initiation complex. Next eIF4 guides the 5’-end (named 5’-cap) of mRNA into the 43S complex and the ribosome proceeds along the mRNA until the start codon is found. Other eIFs then recruit the 60S subunit to create the 80S initiation complex, and synthesis of the polypeptide chain begins.
Nonpolio Enteroviruses, Polioviruses, and Human CNS Infections
Sunit K. Singh, Daniel Růžek in Neuroviral Infections, 2013
In the cytoplasm of the infected cell, a cellular phosphodiesterase removes the Vpg prior to RNA translation. The cellular enzymes are responsable for RNA translation to polyprotein. The 40S ribosomal subunit associates with the IRES and scans the RNA to the initiation codon AUG, where a 60 S ribosomal subunit joins the complex, and elongation of translatation polyprotein occurs. The cleaveage of the eukaryotic translation initiation factor (eIF4G), which is a factor of the initiation complex (eIF4F) by the viral 2A protease, is responsible for the inhibition of cap-dependent initiation of translation. The viral polyprotein is clevead by virus-encoded proteases (2A, 3C, 3CD) into 3 intermediate proteins, Pl, P2, and P3. Protease 2A separates the structural protein Pl from the nonstructural proteins P2 and P3. Protease 3CD cleaves Pl into VPO, VP3, and VP1. The cleavage of VP0 into VP4 and VP2 proteins occurs during viral maturation, and it may be linked to the encapsidation of the RNA. The nonstructural proteins precursors P2 and P3 are separated by 3C/3CD protease into 2A, 2B, 2C, 3A, 3B (Vpg), 3C, and 3D. The viral 2A and 3C proteases mediate the inhibition of cellular RNA synthesis. 3D is an RNA-dependent RNA polymerase necessary for viral RNA synthesis and 2B-C, 3A-B proteins play different roles in viral multiplication.
Co-exposure to silver nanoparticles and cadmium induce metabolic adaptation in HepG2 cells
Published in Nanotoxicology, 2018
Renata Rank Miranda, Vladimir Gorshkov, Barbara Korzeniowska, Stefan J. Kempf, Francisco Filipak Neto, Frank Kjeldsen
To better understand the molecular mechanisms involved in the toxicity of AgNP, Cd2+, and AgNP + Cd2+, protein-protein interaction networks were built using a STRING algorithm for the 24-h exposure experiment (Figure 6), as networks were not formed after 4 h of exposure. AgNP induced the upregulation of mitochondrial proteins related to the respiratory chain and biogenesis of ribosomes, as well as heat shock and cell-cell/matrix adhesion proteins (Figure 6(A)). Multiple proteins involved with translation initiation and ribosome structure were downregulated. Defined clusters of proteins involved in glucose metabolism, antioxidant defense, and cell signaling were also observed (Figure 6(B)). Following the Cd2+ exposure, clusters of protein-protein interactions were only observed for proteins that were downregulated, indicating that nutrient metabolism and depletion of antioxidant defenses were related to the cellular response (Figure 6(C)). Protein-protein interactions in the co-exposure group related more to AgNP than to Cd2+. Upregulation occurred for mitochondrial and respiratory chain proteins, as well as for proteins involved in lipid metabolism, transcription, RNA processing, ribosome formation, and translation (Figure 6(D)). Downregulation occurred for chaperone proteins such as heat shock proteins, proteasome subunits, antioxidant defense proteins, and proteins involved in glycolysis (Figure 6(E)).
Noradrenergic gating of long-lasting synaptic potentiation in the hippocampus: from neurobiology to translational biomedicine
Published in Journal of Neurogenetics, 2018
Peter V. Nguyen, Jennifer N. Gelinas
One important process where various signals and transmitters can act to regulate protein synthesis is at the level of translation initiation, a rate-limiting step in translation of many species of mRNA. Here, different protein kinases act to phosphorylate eukaryotic initiation factors (eIFs) involved in the assembly of translation initiation complexes that promote mRNA binding to ribosomal proteins (Costa-Mattioli et al., 2009). For example, two key protein kinases, extracellular signal-regulated protein kinase (ERK) and mammalian target of rapamycin (mTOR), play an important role in formation of the eukaryotic initiation factor 4F (eIF4F) complex (Gelinas et al., 2007; Kelleher, Govindarajan, & Tonegawa, 2004; Klann, Antion, Banko, & Hou, 2004; Tsokas, Ma, Iyengar, Landau, & Blitzer, 2007). The eIF4F initiation complex is assembled from the initiation factors eIF4A, 4E, and 4 G (Figure 1). In the basal state, formation of eIF4F is restrained by binding of eIF4E to the inhibitory protein, 4E-binding protein (4E-BP) (Banko et al., 2005). Phosphorylation of 4E-BP by mTOR triggers the release of eIF4E, which can then associate with eIF4G and form the eIF4F complex (Figure 1). In addition, ERK phosphorylates and activates the protein kinase, Mnk1 (MAPK signal-integrating kinase-1), which in turn phosphorylates 4E to further enhance translation.
Exercise intervention attenuates neuropathic pain in diabetes via mechanisms of mammalian target of rapamycin (mTOR)
Published in Archives of Physiology and Biochemistry, 2020
Xiaohui Ma, Sitong Liu, Dongxue Liu, Qian Wang, Hongwei Li, Zhen Zhao
The mTOR, which functions in the multiprotein complex mTORC1, is thought to play a role in regulating skeletal muscle protein synthesis and muscle mass (Bodine et al. 2001). Activated mTORC1 can induce muscle protein synthesis through p-S6K1 and p-4E-BP1. This signaling increases ribosomal biogenesis and cap-dependent protein translation initiation (Laplante and Sabatini 2009). In diabetes, it is observed that many stimuli such as growth factors like insulin-like growth factor 1 (IGF-1) can stimulate muscle mTORC1 (Bodine et al. 2001, Inoki et al. 2002). It has also been reported that high glucose and insulin resistance were associated with mTOR activation in diabetes (Brandon et al. 2011, Velagapudi et al. 2011). The mTOR, S6K1, 4E-BP are highly present in DRGs of diabetes, although their active forms are low under normal conditions (Asante et al. 2009, Xu et al. 2010). In addition, it is evidenced that local protein synthesis via the mTOR-depended pathway modulates central peripheral sensitisation and is involved in the development and maintenance of chronic pain states (Asante et al. 2009, Norsted Gregory et al. 2010, Kwon et al. 2017). Pharmacological inhibition of mTOR leads to a decreases in mechanical allodynia via IRS-1(insulin receptor substrate-1)-dependent intracellular signal activation (Obara et al. 2011, Xu et al. 2014).
Related Knowledge Centers
- Activator
- Eukaryotic Initiation Factor
- Protein
- Repressor
- Ribosome
- Start Codon
- Translation
- Protein Biosynthesis
- Eif2
- Eukaryotic Initiation Factor 3