scholarly journals The lin-4 Regulatory RNA Controls Developmental Timing in Caenorhabditis elegans by Blocking LIN-14 Protein Synthesis after the Initiation of Translation

1999 ◽  
Vol 216 (2) ◽  
pp. 671-680 ◽  
Author(s):  
Philip H. Olsen ◽  
Victor Ambros
Keyword(s):  
Protein Synthesis ◽  
Caenorhabditis Elegans ◽  
Developmental Timing ◽  
Regulatory Rna ◽  
Initiation Of Translation

scholarly journals Caspase-mediated cleavage of eukaryotic translation initiation factor subunit 2α

1999 ◽  
Vol 342 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Shinya SATOH ◽  
Makoto HIJIKATA ◽  
Hiroshi HANDA ◽  
Kunitada SHIMOTOHNO
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Caspase 3 ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation Initiation Factor ◽  
Α Subunit ◽  
Eukaryotic Translation ◽  
Initiation Of Translation ◽  
Eukaryotic Translation Initiation

Eukaryotic translation initiation factor 2α (eIF-2α), a target molecule of the interferon-inducible double-stranded-RNA-dependent protein kinase (PKR), was cleaved in apoptotic Saos-2 cells on treatment with poly(I)˙poly(C) or tumour necrosis factor α. This cleavage occurred with a time course similar to that of poly(ADP-ribose) polymerase, a well-known caspase substrate. In addition, eIF-2α was cleaved by recombinant active caspase-3 in vitro. By site-directed mutagenesis, the cleavage site was mapped to an Ala-Glu-Val-Asp300 ↓ Gly301 sequence located in the C-terminal portion of eIF-2α. PKR phosphorylates eIF-2α on Ser51, resulting in the suppression of protein synthesis. PKR-mediated translational suppression was repressed when the C-terminally cleaved product of eIF-2α was overexpressed in Saos-2 cells, even though PKR can phosphorylate this cleaved product. These results suggest that caspase-3 or related protease(s) can modulate the efficiency of protein synthesis by cleaving the α subunit of eIF-2, a key component in the initiation of translation.

Effect of adenovirus on metabolism of specific host mRNAs: transport control and specific translational discrimination

1983 ◽  
Vol 3 (7) ◽  
pp. 1212-1221 ◽  
Author(s):  
A Babich ◽  
L T Feldman ◽  
J R Nevins ◽  
J E Darnell ◽  
C Weinberger
Keyword(s):  
Protein Synthesis ◽  
Host Cell ◽  
Cellular Protein ◽  
Host Protein ◽  
Cell Protein ◽  
Viral Mrna ◽  
Initiation Of Translation ◽  
Viral Mutant ◽  
Cellular Mrnas ◽  
Cellular Protein Synthesis

We have studied the adenovirus-induced inhibition of host cell protein synthesis and the effect of infection on the overall metabolism of host cell mRNA during the late phase of adenovirus infection by following the fate of a number of cellular mRNAs complementary to specific cloned DNA segments. At a time in infection when the rate of total cellular protein synthesis is drastically (greater than 90%) reduced, transcription of specific cellular genes is undiminished. However, the transport of newly synthesized cellular mRNA to the cytoplasm is greatly decreased. This decreased appearance of new mRNA in the cytoplasm cannot account for the observed cessation of cell specific protein synthesis, however, since the concentration of several preexisting cellular mRNAs, including the mRNA for actin, remains unchanged throughout the course of infection. The preexisting mRNA is intact, capped, and functional as judged by its ability to direct protein synthesis in vitro in a cap-dependent fashion. The interruption in host translation appears to operate at the level of initiation directly, since we find that fewer ribosomes are associated with a given cellular mRNA after infection than before infection. Furthermore, the in vivo inhibition of cellular protein synthesis does not appear to be the result of competition with viral mRNA, since conditions which prevent the efficient initiation of translation of viral mRNA (infection with a viral mutant) do not result in the recovery of cell translation. Thus, it appears that a late adenovirus gene product directly mediates a shutoff of host protein synthesis.

Assessment of de novo Protein Synthesis Rates in Caenorhabditis elegans

10.3791/61170 ◽  
2020 ◽  
Author(s):  
Margarita Elena Papandreou ◽  
Konstantinos Palikaras ◽  
Nektarios Tavernarakis
Keyword(s):  
Protein Synthesis ◽  
Caenorhabditis Elegans ◽  
De Novo ◽  
De Novo Protein Synthesis

scholarly journals Sydney Brenner. 13 January 1927—5 April 2019

2020 ◽  
Author(s):  
John White ◽  
Mark S. Bretscher
Keyword(s):  
Protein Synthesis ◽  
Caenorhabditis Elegans ◽  
Genome Analysis ◽  
Genetic Information ◽  
Molecular Biologist ◽  
Model Organisms ◽  
Biological Research ◽  
Neural Function ◽  
Critical Knowledge ◽  
The World

From modest beginnings Sydney became an extraordinarily influential and accomplished molecular biologist. His critical knowledge of, and insights into, key scientific problems were legendary. His irrepressible personality, acerbic wit and ebullient talks inspired a generation of young biologists. He made seminal discoveries in how genetic information is used for protein synthesis, and established Caenorhabditis elegans as one of the foremost model organisms for the study of development and neural function. He also pioneered techniques for genome analysis and was instrumental in establishing several outstanding centres of biological research around the world.

scholarly journals Analysis of a lin-42/period Null Allele Implicates All Three Isoforms in Regulation of Caenorhabditis elegans Molting and Developmental Timing

2016 ◽  
Vol 6 (12) ◽  
pp. 4077-4086 ◽  
Author(s):  
Theresa L B Edelman ◽  
Katherine A McCulloch ◽  
Angela Barr ◽  
Christian Frøkjær-Jensen ◽  
Erik M Jorgensen ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Null Allele ◽  
Postembryonic Development ◽  
Developmental Timing ◽  
Critical Element ◽  
Coding Region ◽  
Protein Coding ◽  
Temporal Regulation ◽  
Larval Stages ◽  
Hypomorphic Alleles

Abstract The Caenorhabditis elegans heterochronic gene pathway regulates the relative timing of events during postembryonic development. lin-42, the worm homolog of the circadian clock gene, period, is a critical element of this pathway. lin-42 function has been defined by a set of hypomorphic alleles that cause precocious phenotypes, in which later developmental events, such as the terminal differentiation of hypodermal cells, occur too early. A subset of alleles also reveals a significant role for lin-42 in molting; larval stages are lengthened and ecdysis often fails in these mutant animals. lin-42 is a complex locus, encoding overlapping and nonoverlapping isoforms. Although existing alleles that affect subsets of isoforms have illuminated important and distinct roles for this gene in developmental timing, molting, and the decision to enter the alternative dauer state, it is essential to have a null allele to understand all of the roles of lin-42 and its individual isoforms. To remedy this problem and discover the null phenotype, we engineered an allele that deletes the entire lin-42 protein-coding region. lin-42 null mutants are homozygously viable, but have more severe phenotypes than observed in previously characterized hypomorphic alleles. We also provide additional evidence for this conclusion by using the null allele as a base for reintroducing different isoforms, showing that each isoform can provide heterochronic and molting pathway activities. Transcript levels of the nonoverlapping isoforms appear to be under coordinate temporal regulation, despite being driven by independent promoters. The lin-42 null allele will continue to be an important tool for dissecting the functions of lin-42 in molting and developmental timing.

Reevaluation of amino acid stimulation of protein synthesis in murine- and human-derived skeletal muscle cells assessed by independent techniques

2005 ◽  
Vol 288 (5) ◽  
pp. E1028-E1037 ◽  
Author(s):  
Britt-Marie Iresjö ◽  
Elisabeth Svanberg ◽  
Kent Lundholm
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Cultured Cells ◽  
Incorporation Rate ◽  
Synthesis Methods ◽  
Distribution Analysis ◽  
Western Blots ◽  
Initiation Factors ◽  
Initiation Of Translation

Murine L6 and human rhabdomyosarcoma cells were cultured standardized in low (0.28 mM) and normal (9 mM) amino acid (AA) concentrations to reevaluate by independent methods to what extent AA activate initiation of protein synthesis. Methods used were incorporation of radioactive AA into proteins, distribution analysis of RNA in density gradient, and Western blots on initiation factors of translation of proteins in cultured cells as well as in vivo (gastrocnemius, C57Bl mice) during starvation/refeeding. Incorporation rate of AA gave incorrect results in a variety of conditions, where phenylalanine stimulated the incorporation rate of phenylalanine into proteins, but not of tyrosine, and tyrosine stimulated incorporation of tyrosine but not of phenylalanine. Similar problems were observed when [35S]methionine was used for labeling of fractionated cellular proteins. However, the methods entirely independent of labeled AA incorporation indicated that essential AA activate initiation of translation, whereas nonessential AA did not. Branched-chain AA and glutamine, in combination with some other AA, also stimulated initiation of translation. Starvation/refeeding in vitro agreed qualitatively with results in vivo evaluated by initiation factors. Insulin at physiological concentrations (100 μM/ml) did not stimulate global protein synthesis at low or normal AA concentrations but did so at supraphysiological levels (3 mU/ml), confirmed by independent methods. Our results reemphasize that labeled AA should be used with caution for quantification of protein synthesis, since the precursor pool(s) for protein synthesis is not in complete equilibrium with surrounding AA. “Flooding” tracee experiments did not overcome this problem.

The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans

Nature ◽  
2000 ◽  
Vol 403 (6772) ◽  
pp. 901-906 ◽  
Author(s):  
Brenda J. Reinhart ◽  
Frank J. Slack ◽  
Michael Basson ◽  
Amy E. Pasquinelli ◽  
Jill C. Bettinger ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Developmental Timing
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