Vertebrate mRNAs with a 5'-terminal pyrimidine tract are candidates for translational repression in quiescent cells: characterization of the translational cis-regulatory element

1994 ◽  
Vol 14 (6) ◽  
pp. 3822-3833
Author(s):  
D Avni ◽  
S Shama ◽  
F Loreni ◽  
O Meyuhas
Keyword(s):  
Translational Control ◽  
Mammalian Cells ◽  
Regulatory Element ◽  
Elongation Factor ◽  
Translational Efficiency ◽  
Translation Control ◽  
Quiescent Cells ◽  
Terminal Oligopyrimidine ◽  
Mode Of Regulation

The translation of mammalian ribosomal protein (rp) mRNAs is selectively repressed in nongrowing cells. This response is mediated through a regulatory element residing in the 5' untranslated region of these mRNAs and includes a 5' terminal oligopyrimidine tract (5' TOP). To further characterize the translational cis-regulatory element, we monitored the translational behavior of various endogenous and heterologous mRNAs or hybrid transcripts derived from transfected chimeric genes. The translational efficiency of these mRNAs was assessed in cells that either were growing normally or were growth arrested under various physiological conditions. Our experiments have yielded the following results: (i) the translation of mammalian rp mRNAs is properly regulated in amphibian cells, and likewise, amphibian rp mRNA is regulated in mammalian cells, indicating that all of the elements required for translation control of rp mRNAs are conserved among vertebrate classes; (ii) selective translational control is not confined to rp mRNAs, as mRNAs encoding the naturally occurring ubiquitin-rp fusion protein and elongation factor 1 alpha, which contain a 5' TOP, also conform this mode of regulation; (iii) rat rpP2 mRNA contains only five pyrimidines in its 5' TOP, yet this mRNA is translationally controlled in the same fashion as other rp mRNAs with a 5' TOP of eight or more pyrimidines; (iv) full manifestation of this mode of regulation seems to require both the 5' TOP and sequences immediately downstream; and (v) an intact translational regulatory element from rpL32 mRNA fails to exert its regulatory properties even when preceded by a single A residue.

scholarly journals Vertebrate mRNAs with a 5'-terminal pyrimidine tract are candidates for translational repression in quiescent cells: characterization of the translational cis-regulatory element.

1994 ◽  
Vol 14 (6) ◽  
pp. 3822-3833 ◽  
Author(s):  
D Avni ◽  
S Shama ◽  
F Loreni ◽  
O Meyuhas
Keyword(s):  
Translational Control ◽  
Mammalian Cells ◽  
Regulatory Element ◽  
Elongation Factor ◽  
Translational Efficiency ◽  
Translation Control ◽  
Quiescent Cells ◽  
Terminal Oligopyrimidine ◽  
Mode Of Regulation

The translation of mammalian ribosomal protein (rp) mRNAs is selectively repressed in nongrowing cells. This response is mediated through a regulatory element residing in the 5' untranslated region of these mRNAs and includes a 5' terminal oligopyrimidine tract (5' TOP). To further characterize the translational cis-regulatory element, we monitored the translational behavior of various endogenous and heterologous mRNAs or hybrid transcripts derived from transfected chimeric genes. The translational efficiency of these mRNAs was assessed in cells that either were growing normally or were growth arrested under various physiological conditions. Our experiments have yielded the following results: (i) the translation of mammalian rp mRNAs is properly regulated in amphibian cells, and likewise, amphibian rp mRNA is regulated in mammalian cells, indicating that all of the elements required for translation control of rp mRNAs are conserved among vertebrate classes; (ii) selective translational control is not confined to rp mRNAs, as mRNAs encoding the naturally occurring ubiquitin-rp fusion protein and elongation factor 1 alpha, which contain a 5' TOP, also conform this mode of regulation; (iii) rat rpP2 mRNA contains only five pyrimidines in its 5' TOP, yet this mRNA is translationally controlled in the same fashion as other rp mRNAs with a 5' TOP of eight or more pyrimidines; (iv) full manifestation of this mode of regulation seems to require both the 5' TOP and sequences immediately downstream; and (v) an intact translational regulatory element from rpL32 mRNA fails to exert its regulatory properties even when preceded by a single A residue.

scholarly journals Molecular evolution of protein-RNA mimicry as a mechanism for translational control

2013 ◽  
Vol 42 (5) ◽  
pp. 3261-3271 ◽  
Author(s):  
Assaf Katz ◽  
Lindsey Solden ◽  
S. Betty Zou ◽  
William Wiley Navarre ◽  
Michael Ibba
Keyword(s):  
Translational Control ◽  
Elongation Factor ◽  
Trna Synthetase ◽  
Post Translational Modification ◽  
Translation Control ◽  
Trna Synthetases ◽  
Ribosome Binding ◽  
Trna Recognition ◽  
Aminoacyl Trna Synthetases ◽  
Secondary Mechanism

Abstract Elongation factor P (EF-P) is a conserved ribosome-binding protein that structurally mimics tRNA to enable the synthesis of peptides containing motifs that otherwise would induce translational stalling, including polyproline. In many bacteria, EF-P function requires post-translational modification with (R)-β-lysine by the lysyl-tRNA synthetase paralog PoxA. To investigate how recognition of EF-P by PoxA evolved from tRNA recognition by aminoacyl-tRNA synthetases, we compared the roles of EF-P/PoxA polar contacts with analogous interactions in a closely related tRNA/synthetase complex. PoxA was found to recognize EF-P solely via identity elements in the acceptor loop, the domain of the protein that interacts with the ribosome peptidyl transferase center and mimics the 3'-acceptor stem of tRNA. Although the EF-P acceptor loop residues required for PoxA recognition are highly conserved, their conservation was found to be independent of the phylogenetic distribution of PoxA. This suggests EF-P first evolved tRNA mimicry to optimize interactions with the ribosome, with PoxA-catalyzed aminoacylation evolving later as a secondary mechanism to further improve ribosome binding and translation control.

Temporal changes in ERK phosphorylation are harmonious with 4E-BP1, but not p70S6K, during clenbuterol-induced hypertrophy in the rat gastrocnemius

2014 ◽  
Vol 39 (8) ◽  
pp. 902-910 ◽  
Author(s):  
Koichiro Sumi ◽  
Seiichiro Higashi ◽  
Midori Natsume ◽  
Keiko Kawahata ◽  
Koichi Nakazato
Keyword(s):  
Translational Control ◽  
Translational Regulation ◽  
Mammalian Target Of Rapamycin ◽  
Elongation Factor ◽  
Muscular Hypertrophy ◽  
Translation Control ◽  
Translational Initiation ◽  
Erk Phosphorylation ◽  
Initiation Of Translation ◽  
Ribosomal S6 Kinase

Extracellular signal-regulated kinase (ERK) is required for clenbuterol (CB)-dependent fast-type myofibril enlargement; however, its contribution to translation control is unclear. ERK mediates translational regulation through mammalian target of rapamycin complex 1 (mTORC1) activation and (or) mTORC1-independent pathways. In this study, we aimed to investigate the role of ERK in translational control during CB-induced muscular hypertrophy by measuring time-dependent changes in the phosphorylation statuses of ERK, p70 ribosomal S6 kinase (p70S6K; an indicator of mTORC1 activity), 4E-binding protein 1 (4E-BP1), eukaryotic elongation factor 2 (eEF2), and other related signaling molecules in rat gastrocnemius muscles. Five-day administration of CB induced phenotypes associated with muscular hypertrophy (significant increases in wet weight and isometric ankle flexion torque in the gastrocnemius muscle), but was not accompanied by elevated ERK or p70S6K phosphorylation. One-day administration of CB caused significant increases in the phosphorylation of ERK, p70S6K, and 4E-BP1. In contrast, 3-day administration of CB caused significant increases in the phosphorylation of ERK and 4E-BP1, but not p70S6K. In addition, positive correlations were observed between ERK and 4E-BP1 on days 1 and 3, whereas a correlation between ERK and p70S6K was only observed on day 1. eEF2 phosphorylation was unchanged on both days 1 and 3. These findings suggest that ERK accelerates the initiation of translation, but does not support the involvement of ERK in translational elongation. Furthermore, ERK may play a major role in promoting translational initiation by mediating the phosphorylation of 4E-BP1, and may contribute to the initial activation of mTORC1 during CB administration.

scholarly journals Apical Na+-d-glucose cotransporter 1 (SGLT1) activity and protein abundance are expressed along the jejunal crypt-villus axis in the neonatal pig

2011 ◽  
Vol 300 (1) ◽  
pp. G60-G70 ◽  
Author(s):  
Chengbo Yang ◽  
David M. Albin ◽  
Zirong Wang ◽  
Barbara Stoll ◽  
Dale Lackeyram ◽  
...  
Keyword(s):  
Translational Control ◽  
Apical Membrane ◽  
Elongation Factor ◽  
Membrane Vesicles ◽  
Maximal Activity ◽  
Initiation Factor ◽  
Translational Efficiency ◽  
Control Mechanisms ◽  
Uptake Activity ◽  
Crypt Cells

Gut apical Na+-glucose cotransporter 1 (SGLT1) activity is high at the birth and during suckling, thus contributing substantially to neonatal glucose homeostasis. We hypothesize that neonates possess high SGLT1 maximal activity by expressing apical SGLT1 protein along the intestinal crypt-villus axis via unique control mechanisms. Kinetics of SGLT1 activity in apical membrane vesicles, prepared from epithelial cells sequentially isolated along the jejunal crypt-villus axis from neonatal piglets by the distended intestinal sac method, were measured. High levels of maximal SGLT1 uptake activity were shown to exist along the jejunal crypt-villus axis in the piglets. Real-time RT-PCR analyses showed that SGLT1 mRNA abundance was lower ( P < 0.05) by 30–35% in crypt cells than in villus cells. There were no significant differences in SGLT1 protein abundances on the jejunal apical membrane among upper villus, middle villus, and crypt cells, consistent with the immunohistochemical staining pattern. Higher abundances ( P < 0.05) of total eukaryotic initiation factor 4E (eIF4E) protein and eIE4E-binding protein 1 γ-isoform in contrast to a lower ( P < 0.05) abundance of phosphorylated (Pi) eukaryotic elongation factor 2 (eEF2) protein and the eEF2-Pi to total eEF2 abundance ratio suggest higher global protein translational efficiency in the crypt cells than in the upper villus cells. In conclusion, neonates have high intestinal apical SGLT1 uptake activity by abundantly expressing SGLT1 protein in the epithelia and on the apical membrane along the entire crypt-villus axis in association with enhanced protein translational control mechanisms in the crypt cells.

scholarly journals Expression and characterization of human antithrombin III synthesized in mammalian cells.

1987 ◽  
Vol 262 (30) ◽  
pp. 14766-14772 ◽  
Author(s):  
L C Wasley ◽  
D H Atha ◽  
K A Bauer ◽  
R J Kaufman
Keyword(s):  
Mammalian Cells ◽  
Antithrombin Iii

scholarly journals Upregulation of 5′-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kyle A. Cottrell ◽  
Ryan C. Chiou ◽  
Jason D. Weber
Keyword(s):  
Protein Synthesis ◽  
Tumor Cells ◽  
Ribosomal Proteins ◽  
Human Cancer ◽  
Mrna Translation ◽  
Ribosome Profiling ◽  
Translational Efficiency ◽  
Gene Encoding ◽  
Terminal Oligopyrimidine ◽  
Ribosome Export

AbstractTumor cells require nominal increases in protein synthesis in order to maintain high proliferation rates. As such, tumor cells must acquire enhanced ribosome production. How the numerous mutations in tumor cells ultimately achieve this aberrant production is largely unknown. The gene encoding ARF is the most commonly deleted gene in human cancer. ARF plays a significant role in regulating ribosomal RNA synthesis and processing, ribosome export into the cytoplasm, and global protein synthesis. Utilizing ribosome profiling, we show that ARF is a major suppressor of 5′-terminal oligopyrimidine mRNA translation. Genes with increased translational efficiency following loss of ARF include many ribosomal proteins and translation factors. Knockout of p53 largely phenocopies ARF loss, with increased protein synthesis and expression of 5′-TOP encoded proteins. The 5′-TOP regulators eIF4G1 and LARP1 are upregulated in Arf- and p53-null cells.

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