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Chembiochem : a European Journal of... May 2020Genetic code expansion (GCE) has revolutionized the field of protein chemistry. Over the past several decades more than 150 different noncanonical amino acids (ncAAs)... (Review)
Review
Genetic code expansion (GCE) has revolutionized the field of protein chemistry. Over the past several decades more than 150 different noncanonical amino acids (ncAAs) have been co-translationally installed into proteins within various host organisms. The vast majority of these ncAAs have been incorporated between the start and stop codons within an open reading frame. This requires that the ncAA be able to form a peptide bond at the α-amine, limiting the types of molecules that can be genetically encoded. In contrast, the α-amine of the initiating amino acid is not required for peptide bond formation. Therefore, including the initiator position in GCE allows for co-translational insertion of more diverse molecules that are modified, or completely lacking an α-amine. This review explores various methods which have been used to initiate protein synthesis with diverse molecules both in vitro and in vivo.
Topics: Amino Acids; Animals; Genetic Code; Humans; Open Reading Frames; Protein Biosynthesis; Protein Engineering; Protein Processing, Post-Translational; Proteins; Synthetic Biology
PubMed: 32023356
DOI: 10.1002/cbic.202000017 -
The New England Journal of Medicine Mar 2023
Review
Topics: Humans; Gene Expression Regulation; Neurodegenerative Diseases; Protein Biosynthesis; RNA; RNA, Messenger
PubMed: 36920757
DOI: 10.1056/NEJMra2215795 -
Annual Review of Genetics Nov 2020As one of the most abundant and conserved RNA species, transfer RNAs (tRNAs) are well known for their role in reading the codons on messenger RNAs and translating them... (Review)
Review
As one of the most abundant and conserved RNA species, transfer RNAs (tRNAs) are well known for their role in reading the codons on messenger RNAs and translating them into proteins. In this review, we discuss the noncanonical functions of tRNAs. These include tRNAs as precursors to novel small RNA molecules derived from tRNAs, also called tRNA-derived fragments, that are abundant across species and have diverse functions in different biological processes, including regulating protein translation, Argonaute-dependent gene silencing, and more. Furthermore, the role of tRNAs in biosynthesis and other regulatory pathways, including nutrient sensing, splicing, transcription, retroelement regulation, immune response, and apoptosis, is reviewed. Genome organization and sequence variation of tRNA genes are also discussed in light of their noncanonical functions. Lastly, we discuss the recent applications of tRNAs in genome editing and microbiome sequencing.
Topics: Animals; Gene Editing; Humans; Protein Biosynthesis; RNA Splicing; RNA, Messenger; RNA, Transfer; Transcription, Genetic
PubMed: 32841070
DOI: 10.1146/annurev-genet-022620-101840 -
Nature Neuroscience Sep 2019
Topics: C9orf72 Protein; Humans; Neurodegenerative Diseases; Nucleotides; Protein Biosynthesis
PubMed: 31427772
DOI: 10.1038/s41593-019-0482-4 -
Journal of Molecular Biology May 2020A large part of mammalian physiology and behaviour shows regular daily variations. This temporal organisation is driven by the activity of an endogenous circadian clock,... (Review)
Review
A large part of mammalian physiology and behaviour shows regular daily variations. This temporal organisation is driven by the activity of an endogenous circadian clock, whose molecular basis consists of diurnal waves in gene expression. Circadian transcription is the major driver of these rhythms, yet post-transcriptional mechanisms, some of which occur in response to systemic cues and in a tissue-specific fashion, have central roles in ultimately establishing the oscillatory gene expression programme as well. Regulatory control that occurs at the level of translation is emerging as an important player in the generation and modulation of protein accumulation rhythms. As a mechanism, translation lies at a privileged position to integrate genetically encoded rhythmic signals with other, external and internal stimuli, including nutrient-derived cues. In this review, we summarise our current knowledge of how diurnal control of translation affects both bulk protein levels and gene-specific protein biosynthesis. We discuss mechanisms of regulation, in particular with regard to the complex interplay between circadian cycles and feeding/fasting cycles, as well as emerging roles for upstream open reading frames in clock control.
Topics: Animals; Circadian Clocks; Circadian Rhythm; Humans; Mammals; Protein Biosynthesis; Transcription, Genetic
PubMed: 32246961
DOI: 10.1016/j.jmb.2020.03.023 -
Oxidative Medicine and Cellular... 2022Cardiovascular disease (CVD) has become a leading cause of mortality and morbidity globally, making it an urgent concern. Although some studies have been performed on... (Review)
Review
Cardiovascular disease (CVD) has become a leading cause of mortality and morbidity globally, making it an urgent concern. Although some studies have been performed on CVD, its molecular mechanism remains largely unknown for all types of CVD. However, recent in vivo and in vitro studies have successfully identified the important roles of posttranslational modifications (PTMs) in various diseases, including CVD. Protein modification, also known as PTMs, refers to the chemical modification of specific amino acid residues after protein biosynthesis, which is a key process that can influence the activity or expression level of proteins. Studies on PTMs have contributed directly to improving the therapeutic strategies for CVD. In this review, we examined recent progress on PTMs and highlighted their importance in both physiological and pathological conditions of the cardiovascular system. Overall, the findings of this review contribute to the understanding of PTMs and their potential roles in the treatment of CVD.
Topics: Cardiovascular Diseases; Humans; Protein Processing, Post-Translational; Proteins
PubMed: 35855865
DOI: 10.1155/2022/3137329 -
The Biochemical Journal Aug 2020Protein segments with a high concentration of positively charged amino acid residues are often used in reporter constructs designed to activate ribosomal mRNA/protein... (Review)
Review
Protein segments with a high concentration of positively charged amino acid residues are often used in reporter constructs designed to activate ribosomal mRNA/protein decay pathways, such as those involving nonstop mRNA decay (NSD), no-go mRNA decay (NGD) and the ribosome quality control (RQC) complex. It has been proposed that the electrostatic interaction of the positively charged nascent peptide with the negatively charged ribosomal exit tunnel leads to translation arrest. When stalled long enough, the translation process is terminated with the degradation of the transcript and an incomplete protein. Although early experiments made a strong argument for this mechanism, other features associated with positively charged reporters, such as codon bias and mRNA and protein structure, have emerged as potent inducers of ribosome stalling. We carefully reviewed the published data on the protein and mRNA expression of artificial constructs with diverse compositions as assessed in different organisms. We concluded that, although polybasic sequences generally lead to lower translation efficiency, it appears that an aggravating factor, such as a nonoptimal codon composition, is necessary to cause translation termination events.
Topics: Base Sequence; Codon; Humans; Poly A; Protein Biosynthesis; Ribosomes
PubMed: 32797214
DOI: 10.1042/BCJ20200303 -
Current Opinion in Plant Biology Oct 2023Transposons are mobile DNA sequences that can move within the genome and integrate in new genomic locations. They are widespread in eukaryotes and prokaryotes and can... (Review)
Review
Transposons are mobile DNA sequences that can move within the genome and integrate in new genomic locations. They are widespread in eukaryotes and prokaryotes and can influence gene expression when landing within or nearby a gene. Although transposon-induced regulation of gene expression at the transcriptional level has been extensively studied, there has been less focus on regulation at the post-transcriptional and translational levels. Recent studies in maize (Zea mays) and other plant species suggest that transposon insertions can affect RNA processing, RNA stability, protein translation and protein stability. We will describe the diverse mechanisms by which transposons can influence gene expression at the post-transcriptional and translational levels, and discuss the interactions between these mechanisms.
Topics: Genes, Plant; Genomics; Protein Biosynthesis; RNA Stability; Zea mays
PubMed: 37619514
DOI: 10.1016/j.pbi.2023.102438 -
Nucleic Acids Research Feb 2020During protein synthesis, translating ribosomes encounter many challenges imposed by various types of defective mRNAs that can lead to reduced cellular fitness and, in... (Review)
Review
During protein synthesis, translating ribosomes encounter many challenges imposed by various types of defective mRNAs that can lead to reduced cellular fitness and, in some cases, even threaten cell viability. Aberrant translation leads to activation of one of several quality control pathways depending on the nature of the problem. These pathways promote the degradation of the problematic mRNA as well as the incomplete translation product, the nascent polypeptide chain. Many of these quality control systems feature critical roles for specialized regulatory factors that work in concert with conventional factors. This review focuses on the mechanisms used by these quality control pathways to recognize aberrant ribosome stalling and discusses the conservation of these systems.
Topics: Peptides; Proteasome Endopeptidase Complex; Protein Biosynthesis; RNA Stability; RNA, Messenger; RNA, Ribosomal; Ribosomes; Ubiquitination
PubMed: 31950154
DOI: 10.1093/nar/gkz1201 -
Cold Spring Harbor Perspectives in... Aug 2019The cellular proteome reflects the total outcome of many regulatory mechanisms that affect the metabolism of messenger RNA (mRNA) along its pathway from synthesis to... (Review)
Review
The cellular proteome reflects the total outcome of many regulatory mechanisms that affect the metabolism of messenger RNA (mRNA) along its pathway from synthesis to degradation. Accumulating evidence in recent years has uncovered the roles of a growing number of mRNA modifications in every step along this pathway, shaping translational output. mRNA modifications affect the translation machinery directly, by influencing translation initiation, elongation and termination, or by altering mRNA levels and subcellular localization. Features of modification-related translational control are described, charting a new and complex layer of translational regulation.
Topics: Adenosine; Animals; Cytidine; Epigenomics; Gene Expression Regulation; Homeostasis; Humans; Methylation; Peptide Chain Elongation, Translational; Peptide Chain Initiation, Translational; Protein Biosynthesis; Pseudouridine; RNA, Messenger; RNA, Transfer; Transcription, Genetic; Transcriptome
PubMed: 30037968
DOI: 10.1101/cshperspect.a032623