scholarly journals Roles of tRNA metabolism in aging and lifespan

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Zheng Zhou ◽  
Bao Sun ◽  
Dongsheng Yu ◽  
Meng Bian
Keyword(s):  
Physiological Function ◽  
Protein Translation ◽  
Biological Research ◽  
Messenger Rnas ◽  
Gradual Decline ◽  
Transfer Rnas ◽  
Trna Modifications ◽  
New Ideas ◽  
Multiple Chronic Diseases ◽  
Trna Derivatives

AbstractTransfer RNAs (tRNAs) mainly function as adapter molecules that decode messenger RNAs (mRNAs) during protein translation by delivering amino acids to the ribosome. Traditionally, tRNAs are considered as housekeepers without additional functions. Nevertheless, it has become apparent from biological research that tRNAs are involved in various physiological and pathological processes. Aging is a form of gradual decline in physiological function that ultimately leads to increased vulnerability to multiple chronic diseases and death. Interestingly, tRNA metabolism is closely associated with aging and lifespan. In this review, we summarize the emerging roles of tRNA-associated metabolism, such as tRNA transcription, tRNA molecules, tRNA modifications, tRNA aminoacylation, and tRNA derivatives, in aging and lifespan, aiming to provide new ideas for developing therapeutics and ultimately extending lifespan in humans.

scholarly journals tRNA Metabolism and Lung Cancer: Beyond Translation

2021 ◽  
Vol 8 ◽  
Author(s):  
Meng Bian ◽  
Shiqiong Huang ◽  
Dongsheng Yu ◽  
Zheng Zhou
Keyword(s):  
Lung Cancer ◽  
Malignant Tumors ◽  
Protein Translation ◽  
Therapeutic Strategies ◽  
High Morbidity ◽  
Health It ◽  
Transfer Rnas ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
New Ideas

Lung cancer, one of the most malignant tumors, has extremely high morbidity and mortality, posing a serious threat to global health. It is an urgent need to fully understand the pathogenesis of lung cancer and provide new ideas for its treatment. Interestingly, accumulating evidence has identified that transfer RNAs (tRNAs) and tRNA metabolism–associated enzymes not only participate in the protein translation but also play an important role in the occurrence and development of lung cancer. In this review, we summarize the different aspects of tRNA metabolism in lung cancer, such as tRNA transcription and mutation, tRNA molecules and derivatives, tRNA-modifying enzymes, and aminoacyl-tRNA synthetases (ARSs), aiming at a better understanding of the pathogenesis of lung cancer and providing new therapeutic strategies for it.

scholarly journals Noncanonical Roles of tRNAs: tRNA Fragments and Beyond

2020 ◽  
Vol 54 (1) ◽  
pp. 47-69 ◽  
Author(s):  
Zhangli Su ◽  
Briana Wilson ◽  
Pankaj Kumar ◽  
Anindya Dutta
Keyword(s):  
Sequence Variation ◽  
Protein Translation ◽  
Nutrient Sensing ◽  
Trna Genes ◽  
Biological Processes ◽  
Messenger Rnas ◽  
Regulatory Pathways ◽  
Transfer Rnas ◽  
Rna Molecules

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.

scholarly journals Inosine in Biology and Disease

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 600
Author(s):  
Sundaramoorthy Srinivasan ◽  
Adrian Gabriel Torres ◽  
Lluís Ribas de Pouplana
Keyword(s):  
Human Health ◽  
Purine Biosynthesis ◽  
Messenger Rnas ◽  
Transfer Rnas ◽  
Functional Roles ◽  
Codon Recognition ◽  
Wobble Position ◽  
Biosynthesis Gene ◽  
The Stability ◽  
Cell Signaling Pathways

The nucleoside inosine plays an important role in purine biosynthesis, gene translation, and modulation of the fate of RNAs. The editing of adenosine to inosine is a widespread post-transcriptional modification in transfer RNAs (tRNAs) and messenger RNAs (mRNAs). At the wobble position of tRNA anticodons, inosine profoundly modifies codon recognition, while in mRNA, inosines can modify the sequence of the translated polypeptide or modulate the stability, localization, and splicing of transcripts. Inosine is also found in non-coding and exogenous RNAs, where it plays key structural and functional roles. In addition, molecular inosine is an important secondary metabolite in purine metabolism that also acts as a molecular messenger in cell signaling pathways. Here, we review the functional roles of inosine in biology and their connections to human health.

scholarly journals Extracurricular Functions of tRNA Modifications in Microorganisms

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 907
Author(s):  
Ashley M. Edwards ◽  
Maame A. Addo ◽  
Patricia C. Dos Santos
Keyword(s):  
Messenger Rna ◽  
Chemical Reactivity ◽  
Trna Synthetase ◽  
Structure Stability ◽  
Cellular Viability ◽  
Aminoacyl Trna Synthetase ◽  
Nutritional Factors ◽  
Transfer Rnas ◽  
Trna Modifications ◽  
Dynamic Landscape

Transfer RNAs (tRNAs) are essential adaptors that mediate translation of the genetic code. These molecules undergo a variety of post-transcriptional modifications, which expand their chemical reactivity while influencing their structure, stability, and functionality. Chemical modifications to tRNA ensure translational competency and promote cellular viability. Hence, the placement and prevalence of tRNA modifications affects the efficiency of aminoacyl tRNA synthetase (aaRS) reactions, interactions with the ribosome, and transient pairing with messenger RNA (mRNA). The synthesis and abundance of tRNA modifications respond directly and indirectly to a range of environmental and nutritional factors involved in the maintenance of metabolic homeostasis. The dynamic landscape of the tRNA epitranscriptome suggests a role for tRNA modifications as markers of cellular status and regulators of translational capacity. This review discusses the non-canonical roles that tRNA modifications play in central metabolic processes and how their levels are modulated in response to a range of cellular demands.

scholarly journals microRNA seedless sites attenuate strong-seed-site-mediated target repression

2019 ◽  
Author(s):  
Xujun Wang ◽  
Jingru Tian ◽  
Peng Cui ◽  
Stephen Mastriano ◽  
Dingyao Zhang ◽  
...  
Keyword(s):  
Protein Translation ◽  
Untranslated Regions ◽  
Seed Region ◽  
Biological Processes ◽  
Messenger Rnas ◽  
Protein Coding ◽  
Attenuation Effect ◽  
Reporter Assays ◽  
Regulate Protein ◽  
Surprising Finding

AbstractMicroRNAs (miRNAs) regulate protein-coding gene expression primarily through cognitive binding sites in the 3’ untranslated regions (3′ UTRs). Seed sites are sequences in messenger RNAs (mRNAs) that form perfect Watson-Crick base-paring with a miRNA’s seed region, which can effectively reduce mRNA abundance and/or repress protein translation. Some seedless sites, which do no form perfect seed-pairing with a miRNA, can also lead to target repression, often with lower efficacy. Here we report the surprising finding that when seedless sites and seed sites are co-present in the same 3’UTR, seedless sites attenuate strong-seed-site-mediated target suppression, independent of 3′ UTR length. This attenuation effect is detectable in >70% of transcriptomic datasets examined, in which specific miRNAs are experimentally increased or decreased. The attenuation effect is confirmed by 3’UTR reporter assays and mediated through base-pairing between miRNA and seedless sites. Furthermore, this seedless-site-based attenuation effect could affect seed sites of the same miRNA or another miRNA, thus partially explaining the variability in target suppression and miRNA-mediated gene upregulation. Our findings reveal an unexpected principle of miRNA-mediated gene regulation, and could impact the understanding of many miRNA-regulated biological processes.

scholarly journals Cell Cycle Control by Nuclear Sequestration ofCDC20andCDH1mRNA in Plant Stem Cells

2017 ◽  
Author(s):  
Weibing Yang ◽  
Raymond Wightman ◽  
Elliot M. Meyerowitz
Keyword(s):  
Cell Cycle ◽  
Nuclear Localization ◽  
Cell Cycle Control ◽  
Protein Translation ◽  
Messenger Rnas ◽  
Protein Coding ◽  
Rna Molecules ◽  
Nuclear Envelope Breakdown ◽  
And Function ◽  
Necessary And Sufficient

AbstractIn eukaryotic cells, most RNA molecules are exported into the cytoplasm after being transcribed in the nucleus. Long noncoding RNAs (lncRNAs) have been found to reside and function primarily inside the nucleus, but nuclear localization of protein-coding messenger RNAs (mRNAs) has been considered rare in both animals and plants. Here we show that two mRNAs, transcribed from theCDC20andCCS52B(plant orthologue ofCDH1) genes, are specifically sequestered inside the nucleus during the cell cycle. CDC20 and CDH1 both function as coactivators of the anaphase-promoting complex or cyclosome (APC/C) E3 ligase to trigger cyclin B (C YCB) destruction. In theArabidopsis thalianashoot apical meristem (SAM), we findCDC20andCCS52Bare co-expressed withCYCBsin mitotic cells.CYCBtranscripts can be exported and translated, whereasCDC20andCCS52BmRNAs are strictly confined to the nucleus at prophase and the cognate proteins are not translated until the redistribution of the mRNAs to the cytoplasm after nuclear envelope breakdown (NEBD) at prometaphase. The 5’ untranslated region (UTR) is necessary and sufficient forCDC20mRNA nuclear localization as well as protein translation. Mitotic enrichment ofCDC20andCCS52Btranscripts enables the timely and rapid activation of APC/C, while their nuclear sequestration at prophase appears to protect cyclins from precocious degradation.

scholarly journals microRNAs Mediated Regulation of the Ribosomal Proteins and its Consequences on the Global Translation of Proteins

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 110
Author(s):  
Abu Musa Md Talimur Reza ◽  
Yu-Guo Yuan
Keyword(s):  
Gene Expression ◽  
Untranslated Region ◽  
Ribosomal Proteins ◽  
Protein Translation ◽  
Messenger Rnas ◽  
Coding Region ◽  
Rna Helicases ◽  
Energy Consuming ◽  
Enzyme Families ◽  
Aaa Atpases

Ribosomal proteins (RPs) are mostly derived from the energy-consuming enzyme families such as ATP-dependent RNA helicases, AAA-ATPases, GTPases and kinases, and are important structural components of the ribosome, which is a supramolecular ribonucleoprotein complex, composed of Ribosomal RNA (rRNA) and RPs, coordinates the translation and synthesis of proteins with the help of transfer RNA (tRNA) and other factors. Not all RPs are indispensable; in other words, the ribosome could be functional and could continue the translation of proteins instead of lacking in some of the RPs. However, the lack of many RPs could result in severe defects in the biogenesis of ribosomes, which could directly influence the overall translation processes and global expression of the proteins leading to the emergence of different diseases including cancer. While microRNAs (miRNAs) are small non-coding RNAs and one of the potent regulators of the post-transcriptional gene expression, miRNAs regulate gene expression by targeting the 3′ untranslated region and/or coding region of the messenger RNAs (mRNAs), and by interacting with the 5′ untranslated region, and eventually finetune the expression of approximately one-third of all mammalian genes. Herein, we highlighted the significance of miRNAs mediated regulation of RPs coding mRNAs in the global protein translation.

scholarly journals CD4+ T-Cell Activation Prompts Suppressive Function by Extracellular Vesicle-Associated MicroRNAs

2021 ◽  
Vol 9 ◽  
Author(s):  
Dario Di Silvestre ◽  
Silvia Garavelli ◽  
Claudio Procaccini ◽  
Francesco Prattichizzo ◽  
Giulia Passignani ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Transcriptional Repression ◽  
Cell Activation ◽  
Cell Activity ◽  
Protein Translation ◽  
Cell Receptor ◽  
Effector Function ◽  
Energy Utilization ◽  
Messenger Rnas

MicroRNAs (miRNAs), small non-coding molecules targeting messenger RNAs and inhibiting protein translation, modulate key biological processes, including cell growth and development, energy utilization, and homeostasis. In particular, miRNAs control the differentiation, survival, and activation of CD4+ T conventional (Tconv) cells, key players of the adaptive immunity, and regulate the physiological response to infections and the pathological loss of immune homeostasis in autoimmunity. Upon T-cell receptor (TCR) stimulation, the described global miRNA quantitative decrease occurring in T cells is believed to promote the acquisition of effector functions by relaxing the post-transcriptional repression of genes associated with proliferation and cell activity. MiRNAs were initially thought to get downregulated uniquely by intracellular degradation; on the other hand, miRNA secretion via extracellular vesicles (EVs) represents an additional mechanism of rapid downregulation. By focusing on molecular interactions by means of graph theory, we have found that miRNAs released by TCR-stimulated Tconv cells are significantly enriched for targeting transcripts upregulated upon stimulation, including those encoding for crucial proteins associated with Tconv cell activation and function. Based on this computational approach, we present our perspective based on the following hypothesis: a stimulated Tconv cell will release miRNAs targeting genes associated with the effector function in the extracellular space in association with EVs, which will thus possess a suppressive potential toward other Tconv cells in the paracrine environment. We also propose possible future directions of investigation aimed at taking advantage of these phenomena to control Tconv cell effector function in health and autoimmunity.

scholarly journals The Reading Frame Surveillance Hypothesis

2016 ◽  
Author(s):  
John T. Gray
Keyword(s):  
Large Subunit ◽  
Protein Translation ◽  
Small Subunit ◽  
Phenotypic Traits ◽  
Biological Processes ◽  
Messenger Rnas ◽  
Protein Coding ◽  
Reading Frame ◽  
Mammalian Sperm ◽  
Translation Mechanism

AbbreviationsRFSReading Frame SurveillanceRdRPRNA-dependent RNA PolymerasefrRNAsFraming RNAsLSULarge SubunitSSUSmall SubunittRFTransfer RNA derived FragmentntnucleotideAbstractAn alternative model for protein translation is presented wherein ribosomes utilize a complementary RNA copy of protein coding sequences to monitor the progress of messenger RNAs during their translation to reduce the frequency of frameshifting errors. The synthesis of this ‘framing RNA’ is postulated to be catalyzed by the small subunit of the ribosome, in the decoding center, by excising and concatemerizing tRNA anticodons bound to each codon of the mRNA template. Various components of the model are supported by previous observations of tRNA mutants that impact ribosomal frameshifting, unique globin-coding RNAs in developing erythroblasts, and the epigenetic, intergenerational transfer of phenotypic traits via mammalian sperm RNA. Confirmation of the proposed translation mechanism is experimentally tractable and might significantly enhance our understanding of several fundamental biological processes.

scholarly journals Genome recoding by tRNA modifications

Open Biology ◽  
2016 ◽  
Vol 6 (12) ◽  
pp. 160287 ◽  
Author(s):  
Francesca Tuorto ◽  
Frank Lyko
Keyword(s):  
Protein Translation ◽  
Eukaryotic Genome ◽  
Protein Homeostasis ◽  
Anticodon Loop ◽  
Rna Modifications ◽  
Cellular Adaptation ◽  
Rna Sequence ◽  
Trna Modifications ◽  
Functional Relevance

RNA modifications are emerging as an additional regulatory layer on top of the primary RNA sequence. These modifications are particularly enriched in tRNAs where they can regulate not only global protein translation, but also protein translation at the codon level. Modifications located in or in the vicinity of tRNA anticodons are highly conserved in eukaryotes and have been identified as potential regulators of mRNA decoding. Recent studies have provided novel insights into how these modifications orchestrate the speed and fidelity of translation to ensure proper protein homeostasis. This review highlights the prominent modifications in the tRNA anticodon loop: queuosine, inosine, 5-methoxycarbonylmethyl-2-thiouridine, wybutosine, threonyl–carbamoyl–adenosine and 5-methylcytosine. We discuss the functional relevance of these modifications in protein translation and their emerging role in eukaryotic genome recoding during cellular adaptation and disease.

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