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Current Opinion in Clinical Nutrition... Jan 2015To highlight the recent evicence for optimal protein intake and protein supplementation in older adults. A special focus has been placed on the effects on muscle protein... (Review)
Review
PURPOSE OF REVIEW
To highlight the recent evicence for optimal protein intake and protein supplementation in older adults. A special focus has been placed on the effects on muscle protein synthesis, strength and overall performance in this population.
RECENT FINDINGS
Although for older adults, some additional evidence on the benefits of a higher protein intake than 0.8 g/kg body weight per day has been provided, the results of studies focusing on the timing of protein intake over the day have been contradictory. Supplementation with so-called 'fast' proteins, which are also rich in leucine, for example whey protein, proved superior with regard to muscle protein synthesis. First studies in frail older persons showed increased strength after supplementation with milk protein, whereas the combination with physical exercise increased muscle mass without additional benefit for strength or functionality.
SUMMARY
Recent evidence suggests positive effects of protein supplementation on muscle protein synthesis, muscle mass and muscle strength. However, as most studies included only small numbers of participants for short treatment periods, larger studies with longer duration are necessary to support the clinical relevance of these observations.
Topics: Aging; Dietary Proteins; Dietary Supplements; Exercise; Humans; Muscle Proteins; Muscle Strength; Muscle, Skeletal; Protein Biosynthesis
PubMed: 25474010
DOI: 10.1097/MCO.0000000000000124 -
Cell Systems Jun 2021Molecular translation systems provide a genetically encoded framework for protein synthesis, which is essential for all life. Engineering these systems to incorporate... (Review)
Review
Molecular translation systems provide a genetically encoded framework for protein synthesis, which is essential for all life. Engineering these systems to incorporate non-canonical amino acids (ncAAs) into peptides and proteins has opened many exciting opportunities in chemical and synthetic biology. Here, we review recent advances that are transforming our ability to engineer molecular translation systems. In cell-based systems, new processes to synthesize recoded genomes, tether ribosomal subunits, and engineer orthogonality with high-throughput workflows have emerged. In cell-free systems, adoption of flexizyme technology and cell-free ribosome synthesis and evolution platforms are expanding the limits of chemistry at the ribosome's RNA-based active site. Looking forward, innovations will deepen understanding of molecular translation and provide a path to polymers with previously unimaginable structures and functions.
Topics: Amino Acids; Cell-Free System; Protein Biosynthesis; Proteins; Synthetic Biology
PubMed: 34139167
DOI: 10.1016/j.cels.2021.04.001 -
Nucleic Acids Research Feb 2020During canonical translation, the ribosome moves along an mRNA from the start to the stop codon in exact steps of one codon at a time. The collinearity of the mRNA and... (Review)
Review
During canonical translation, the ribosome moves along an mRNA from the start to the stop codon in exact steps of one codon at a time. The collinearity of the mRNA and the protein sequence is essential for the quality of the cellular proteome. Spontaneous errors in decoding or translocation are rare and result in a deficient protein. However, dedicated recoding signals in the mRNA can reprogram the ribosome to read the message in alternative ways. This review summarizes the recent advances in understanding the mechanisms of three types of recoding events: stop-codon readthrough, -1 ribosome frameshifting and translational bypassing. Recoding events provide insights into alternative modes of ribosome dynamics that are potentially applicable to other non-canonical modes of prokaryotic and eukaryotic translation.
Topics: Codon, Terminator; Frameshifting, Ribosomal; Protein Biosynthesis; Ribosomes
PubMed: 31511883
DOI: 10.1093/nar/gkz783 -
Molecular Cell Apr 2021Eukaryotic cells integrate multiple quality control (QC) responses during protein synthesis in the cytoplasm. These QC responses are signaled by slow or stalled... (Review)
Review
Eukaryotic cells integrate multiple quality control (QC) responses during protein synthesis in the cytoplasm. These QC responses are signaled by slow or stalled elongating ribosomes. Depending on the nature of the delay, the signal may lead to translational repression, messenger RNA decay, ribosome rescue, and/or nascent protein degradation. Here, we discuss how the structure and composition of an elongating ribosome in a troubled state determine the downstream quality control pathway(s) that ensue. We highlight the intersecting pathways involved in RNA decay and the crosstalk that occurs between RNA decay and ribosome rescue.
Topics: Animals; Eukaryotic Cells; Humans; Protein Biosynthesis; RNA Stability; RNA, Messenger; Ribosomes
PubMed: 33713598
DOI: 10.1016/j.molcel.2021.02.022 -
Journal of Molecular Biology May 2016The elongation phase of protein synthesis defines the overall speed and fidelity of protein synthesis and affects protein folding and targeting. The mechanisms of... (Review)
Review
The elongation phase of protein synthesis defines the overall speed and fidelity of protein synthesis and affects protein folding and targeting. The mechanisms of reactions taking place during translation elongation remain important questions in understanding ribosome function. The ribosome-guided by signals in the mRNA-can recode the genetic information, resulting in alternative protein products. Co-translational protein folding and interaction of ribosomes and emerging polypeptides with associated protein biogenesis factors determine the quality and localization of proteins. In this review, we summarize recent findings on mechanisms of translation elongation in bacteria, including decoding and recoding, peptide bond formation, tRNA-mRNA translocation, co-translational protein folding, interaction with protein biogenesis factors and targeting of ribosomes synthesizing membrane proteins to the plasma membrane. The data provide insights into how the ribosome shapes composition and quality of the cellular proteome.
Topics: Bacteria; Humans; Peptide Chain Elongation, Translational; Protein Biosynthesis; Protein Folding; RNA, Messenger; RNA, Transfer; Ribosomes
PubMed: 27038507
DOI: 10.1016/j.jmb.2016.03.022 -
Trends in Biochemical Sciences Sep 2021Ribosomes that stall inappropriately during protein synthesis harbor proteotoxic components linked to cellular stress and neurodegenerative diseases. Molecular... (Review)
Review
Ribosomes that stall inappropriately during protein synthesis harbor proteotoxic components linked to cellular stress and neurodegenerative diseases. Molecular mechanisms that rescue stalled ribosomes must selectively detect rare aberrant translational complexes and process the heterogeneous components. Ribosome-associated quality control pathways eliminate problematic messenger RNAs and nascent proteins on stalled translational complexes. In addition, recent studies have uncovered general principles of stall recognition upstream of quality control pathways and fail-safe mechanisms that ensure nascent proteome integrity. Here, we discuss developments in our mechanistic understanding of the detection and rescue of stalled ribosomal complexes in eukaryotes.
Topics: Protein Biosynthesis; Protein Processing, Post-Translational; Proteins; RNA, Messenger; Ribosomes
PubMed: 33966939
DOI: 10.1016/j.tibs.2021.03.008 -
Molecular Cell Aug 2018The billions of proteins inside a eukaryotic cell are organized among dozens of sub-cellular compartments, within which they are further organized into protein... (Review)
Review
The billions of proteins inside a eukaryotic cell are organized among dozens of sub-cellular compartments, within which they are further organized into protein complexes. The maintenance of both levels of organization is crucial for normal cellular function. Newly made proteins that fail to be segregated to the correct compartment or assembled into the appropriate complex are defined as orphans. In this review, we discuss the challenges faced by a cell of minimizing orphaned proteins, the quality control systems that recognize orphans, and the consequences of excess orphans for protein homeostasis and disease.
Topics: Protein Biosynthesis; Protein Transport; Proteins; Proteolysis; Proteostasis
PubMed: 30075143
DOI: 10.1016/j.molcel.2018.07.001 -
Cold Spring Harbor Perspectives in... Dec 2018More than 40 different neurological diseases are caused by microsatellite repeat expansions that locate within translated or untranslated gene regions, including 5' and... (Review)
Review
More than 40 different neurological diseases are caused by microsatellite repeat expansions that locate within translated or untranslated gene regions, including 5' and 3' untranslated regions (UTRs), introns, and protein-coding regions. Expansion mutations are transcribed bidirectionally and have been shown to give rise to proteins, which are synthesized from three reading frames in the absence of an AUG initiation codon through a novel process called repeat-associated non-ATG (RAN) translation. RAN proteins, which were first described in spinocerebellar ataxia type 8 (SCA8) and myotonic dystrophy type 1 (DM1), have now been reported in a growing list of microsatellite expansion diseases. This article reviews what is currently known about RAN proteins in microsatellite expansion diseases and experiments that provide clues on how RAN translation is regulated.
Topics: Central Nervous System Diseases; Genetic Predisposition to Disease; Humans; Microsatellite Repeats; Protein Biosynthesis
PubMed: 29891563
DOI: 10.1101/cshperspect.a033019 -
Aging Dec 2018Aging is characterized by the accumulation of damage and other deleterious changes, leading to the loss of functionality and fitness. Age-related changes occur at most... (Review)
Review
Aging is characterized by the accumulation of damage and other deleterious changes, leading to the loss of functionality and fitness. Age-related changes occur at most levels of organization of a living organism (molecular, organellar, cellular, tissue and organ). However, protein synthesis is a major biological process, and thus understanding how it changes with age is of paramount importance. Here, we discuss the relationships between lifespan, aging, protein synthesis and translational control, and expand this analysis to the various aspects of proteome behavior in organisms with age. Characterizing the consequences of changes in protein synthesis and translation fidelity, and determining whether altered translation is pathological or adaptive is necessary for understanding the aging process, as well as for developing approaches to target dysfunction in translation as a strategy for extending lifespan.
Topics: Aging; Gene Expression Regulation; Humans; Protein Biosynthesis; Proteome
PubMed: 30562164
DOI: 10.18632/aging.101721 -
Advances in Cancer Research 2017
Topics: Animals; Genome; Humans; MicroRNAs; Neoplasms; Protein Biosynthesis; RNA, Untranslated
PubMed: 28882226
DOI: 10.1016/S0065-230X(17)30034-9