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Cold Spring Harbor Perspectives in... May 2019Stress granules (SGs) and processing bodies (PBs) are non-membrane-enclosed RNA granules that dynamically sequester translationally inactive messenger ribonucleoprotein... (Review)
Review
Stress granules (SGs) and processing bodies (PBs) are non-membrane-enclosed RNA granules that dynamically sequester translationally inactive messenger ribonucleoprotein particles (mRNPs) into compartments that are distinct from the surrounding cytoplasm. mRNP remodeling, silencing, and/or storage involves the dynamic partitioning of closed-loop polyadenylated mRNPs into SGs, or the sequestration of deadenylated, linear mRNPs into PBs. SGs form when stress-activated pathways stall translation initiation but allow elongation and termination to occur normally, resulting in a sudden excess of mRNPs that are spatially condensed into discrete foci by protein:protein, protein:RNA, and RNA:RNA interactions. In contrast, PBs can exist in the absence of stress, when specific factors promote mRNA deadenylation, condensation, and sequestration from the translational machinery. The formation and dissolution of SGs and PBs reflect changes in messenger RNA (mRNA) metabolism and allow cells to modulate the proteome and/or mediate life or death decisions during changing environmental conditions.
Topics: Animals; Cytoplasmic Granules; Gene Expression Regulation; Protein Biosynthesis; Ribonucleoproteins
PubMed: 30082464
DOI: 10.1101/cshperspect.a032813 -
Molecular Biology, Biochemistry, and... 1979
Review
Topics: Animals; Anti-Bacterial Agents; Guanosine Triphosphate; Peptide Chain Elongation, Translational; Peptide Chain Initiation, Translational; Peptide Chain Termination, Translational; Peptide Initiation Factors; Protein Biosynthesis; RNA, Transfer; Ribosomes; Structure-Activity Relationship
PubMed: 370549
DOI: 10.1007/978-3-642-81309-2 -
Cold Spring Harbor Perspectives in... Oct 2018Termination of mRNA translation occurs when a stop codon enters the A site of the ribosome, and in eukaryotes is mediated by release factors eRF1 and eRF3, which form a... (Review)
Review
Termination of mRNA translation occurs when a stop codon enters the A site of the ribosome, and in eukaryotes is mediated by release factors eRF1 and eRF3, which form a ternary eRF1/eRF3-guanosine triphosphate (GTP) complex. eRF1 recognizes the stop codon, and after hydrolysis of GTP by eRF3, mediates release of the nascent peptide. The post-termination complex is then disassembled, enabling its constituents to participate in further rounds of translation. Ribosome recycling involves splitting of the 80S ribosome by the ATP-binding cassette protein ABCE1 to release the 60S subunit. Subsequent dissociation of deacylated transfer RNA (tRNA) and messenger RNA (mRNA) from the 40S subunit may be mediated by initiation factors (priming the 40S subunit for initiation), by ligatin (eIF2D) or by density-regulated protein (DENR) and multiple copies in T-cell lymphoma-1 (MCT1). These events may be subverted by suppression of termination (yielding carboxy-terminally extended read-through polypeptides) or by interruption of recycling, leading to reinitiation of translation near the stop codon.
Topics: Eukaryotic Cells; Peptide Termination Factors; Protein Biosynthesis; Protein Conformation; RNA, Messenger; Ribosomes
PubMed: 29735640
DOI: 10.1101/cshperspect.a032656 -
Journal of Molecular Cell Biology Oct 2019Most eukaryotic mRNAs are translated in a cap-dependent fashion; however, under stress conditions, the cap-independent translation driven by internal ribosomal entry... (Review)
Review
Most eukaryotic mRNAs are translated in a cap-dependent fashion; however, under stress conditions, the cap-independent translation driven by internal ribosomal entry sites (IRESs) can serve as an alternative mechanism for protein production. Many IRESs have been discovered from viral or cellular mRNAs to promote ribosome assembly and initiate translation by recruiting different trans-acting factors. Although the mechanisms of translation initiation driven by viral IRESs are relatively well understood, the existence of cellular IRESs is still under debate due to the limitations of translation reporter systems used to assay IRES activities. A recent screen identified > 1000 putative IRESs from viral and human mRNAs, expanding the scope and mechanism for cap-independent translation. Additionally, a large number of circular RNAs lacking free ends were identified in eukaryotic cells, many of which are found to be translated through IRESs. These findings suggest that IRESs may play a previously unappreciated role in driving translation of the new type of mRNA, implying a hidden proteome produced from cap-independent translation.
Topics: Humans; Internal Ribosome Entry Sites; Models, Biological; Protein Biosynthesis; Proteome; Ribosomes
PubMed: 31504667
DOI: 10.1093/jmcb/mjz091 -
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 -
Annual Review of Biochemistry 1973
Review
Topics: Peptide Biosynthesis; Peptide Chain Elongation, Translational; Peptide Chain Initiation, Translational; Peptide Chain Termination, Translational; Peptide Elongation Factors; Peptide Initiation Factors; Phosphoproteins; Protein Biosynthesis; RNA, Messenger; RNA, Transfer; Ribosomes
PubMed: 4581230
DOI: 10.1146/annurev.bi.42.070173.002145 -
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 -
Biochemistry. Biokhimiia Aug 2006This review highlights studies by Lev L. Kisselev and his colleagues on the initial and terminal stages of protein biosynthesis, which cover the period of the last 45... (Review)
Review
This review highlights studies by Lev L. Kisselev and his colleagues on the initial and terminal stages of protein biosynthesis, which cover the period of the last 45 years (1961-2006). They investigated spatial structure of tRNAs, structure and functions of aminoacyl-tRNA-synthetases of higher organisms, and the final step of protein synthesis, termination of translation. L. Kisselev and his team have made three major contributions to these fields of molecular biology; (i) they proposed the hypothesis on the role of anticodon triplet of tRNA in recognition by cognate aminoacyl-tRNA synthetase, which has been experimentally confirmed and is now included in textbooks; (ii) identified primary structures and functions of two eukaryotic protein factors (eRF1 and eRF3) playing a pivotal role in translation termination; (iii) characterized a structural basis for stop codon recognition by eRF1 within the ribosome and discovered the negative structural elements of eRF1, limiting its recognition of one or two stop-codons.
Topics: Amino Acyl-tRNA Synthetases; History, 20th Century; History, 21st Century; Peptide Chain Initiation, Translational; Peptide Chain Termination, Translational; Peptide Termination Factors; Protein Biosynthesis; RNA, Transfer
PubMed: 16978156
DOI: 10.1134/s0006297906080141 -
Trends in Biochemical Sciences Apr 2020The collection of chemically different protein variants, or proteoforms, by far exceeds the number of protein-coding genes in the human genome. Major contributors are... (Review)
Review
The collection of chemically different protein variants, or proteoforms, by far exceeds the number of protein-coding genes in the human genome. Major contributors are alternative splicing and protein modifications. In this review, we focus on those proteoforms that differ at their N termini with a molecular link to disease. We describe the main underlying mechanisms that give rise to such N-terminal proteoforms, these being splicing, initiation of protein translation, and protein modifications. Given their role in several human diseases, it is becoming increasingly clear that several of these N-terminal proteoforms may have potential as therapeutic interventions and/or for diagnosing and prognosing their associated disease.
Topics: Alternative Splicing; Humans; Protein Biosynthesis; Protein Processing, Post-Translational
PubMed: 32001092
DOI: 10.1016/j.tibs.2019.12.009 -
Cell Reports Jan 2016The economy of protein production is central to cell physiology, being intimately linked with cell division rate and cell size. Attempts to model cellular physiology are...
The economy of protein production is central to cell physiology, being intimately linked with cell division rate and cell size. Attempts to model cellular physiology are limited by the scarcity of experimental data defining the molecular processes limiting protein expression. Here, we distinguish the relative contribution of gene transcription and protein translation to the slower proliferation of budding yeast producing excess levels of unneeded proteins. In contrast to widely held assumptions, rapidly growing cells are not universally limited by ribosome content. Rather, transcription dominates cost under some conditions (e.g., low phosphate), translation in others (e.g., low nitrogen), and both in other conditions (e.g., rich media). Furthermore, cells adapted to enforced protein production by becoming larger and increasing their endogenous protein levels, suggesting limited competition for common resources. We propose that rapidly growing cells do not exhaust their resources to maximize growth but maintain sufficient reserves to accommodate changing requirements.
Topics: Gene Expression Regulation, Fungal; Protein Biosynthesis; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Transcription, Genetic
PubMed: 26725116
DOI: 10.1016/j.celrep.2015.12.015