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

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.

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1118
Author(s):  
Chhavi Choudhary ◽  
Shivasmi Sharma ◽  
Keshav Kumar Meghwanshi ◽  
Smit Patel ◽  
Prachi Mehta ◽  
...  

Only a small subset of all the transcribed RNAs are used as a template for protein translation, whereas RNA molecules that are not translated play a very important role as regulatory non-coding RNAs (ncRNAs). Besides traditionally known RNAs (ribosomal and transfer RNAs), ncRNAs also include small non-coding RNAs (sncRNAs) and long non-coding RNAs (lncRNAs). The lncRNAs, which were initially thought to be junk, have gained a great deal attention because of their regulatory roles in diverse biological processes in animals and plants. Insects are the most abundant and diverse group of animals on this planet. Recent studies have demonstrated the role of lncRNAs in almost all aspects of insect development, reproduction, and genetic plasticity. In this review, we describe the function and molecular mechanisms of the mode of action of different insect lncRNAs discovered up to date.


Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 902
Author(s):  
Eva Costanzi ◽  
Carolina Simioni ◽  
Gabriele Varano ◽  
Cinzia Brenna ◽  
Ilaria Conti ◽  
...  

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.


2019 ◽  
Author(s):  
Xujun Wang ◽  
Jingru Tian ◽  
Peng Cui ◽  
Stephen Mastriano ◽  
Dingyao Zhang ◽  
...  

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.


2017 ◽  
Author(s):  
Weibing Yang ◽  
Raymond Wightman ◽  
Elliot M. Meyerowitz

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.


2021 ◽  
Vol 01 (1) ◽  
pp. 9-15
Author(s):  
Imad Matouk

Increasing evidence has indicated that the non-coding RNA molecules play central roles in almost all biological processes and many pathological conditions including carcinogenesis. This review focuses on the pathological tumorigenic role of the first discovered long non-coding RNA gene called H19 and its pivotal contribution to the cancer axis of evil. H19 RNA utilizes a variety of mechanisms to perform its pathological function. Some key unanswered questions are presented by the end. Understanding the H19 RNA mechanisms of action will shed light into the class of long non-coding RNA which contains thousands of members mostly with unknown function and will help in delineating the pathological role played by at least some of them.


2004 ◽  
Vol 186 (24) ◽  
pp. 8472-8477 ◽  
Author(s):  
Yngve Östberg ◽  
Ignas Bunikis ◽  
Sven Bergström ◽  
Jörgen Johansson

ABSTRACT Small regulatory RNAs (sRNAs) have recently been shown to be the main controllers of several regulatory pathways. The function of sRNAs depends in many cases on the RNA-binding protein Hfq, especially for sRNAs with an antisense function. In this study, the genome of Borrelia burgdorferi was subjected to different searches for sRNAs, including direct homology and comparative genomics searches and ortholog- and annotation-based search strategies. Two new sRNAs were found, one of which showed complementarity to the rpoS region, which it possibly controls by an antisense mechanism. The role of the other sRNA is unknown, although observed complementarities against particular mRNA sequences suggest an antisense mechanism. We suggest that the low level of sRNAs observed in B. burgdorferi is at least partly due to the presumed lack of both functional Hfq protein and RNase E activity.


2011 ◽  
Vol 43 (10) ◽  
pp. 543-556 ◽  
Author(s):  
Jaideep Banerjee ◽  
Yuk Cheung Chan ◽  
Chandan K. Sen

MicroRNAs (miRNAs) are small endogenous RNA molecules ∼22 nt in length. miRNAs are capable of posttranscriptional gene regulation by binding to their target messenger RNAs (mRNAs), leading to mRNA degradation or suppression of translation. miRNAs have recently been shown to play pivotal roles in skin development and are linked to various skin pathologies, cancer, and wound healing. This review focuses on the role of miRNAs in cutaneous biology, the various methods of miRNA modulation, and the therapeutic opportunities in treatment of skin diseases and wound healing.


2016 ◽  
Author(s):  
John T. Gray

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.


Author(s):  
Sunil Kumar ◽  
Muhammad Umer Ashraf ◽  
Anil Kumar ◽  
Yong-Soo Bae

: MicroRNAs (miRNAs) are short ~18-22 nucleotide, single-stranded, non-coding RNA molecules playing a crucial role in regulating diverse biological processes, and are frequently dysregulated during disease pathogenesis. Thus, targeting miRNA could be a potential candidate for therapeutic invention. This systemic review aims to summarize our current understanding regarding the role of miRNAs associated with Th2-mediated immune disorders and strategies for therapeutic drug development and current clinical trials.


2019 ◽  
Vol 25 (6) ◽  
pp. 642-653 ◽  
Author(s):  
Uzma Zaheer ◽  
Muhammed Faheem ◽  
Ishtiaq Qadri ◽  
Nargis Begum ◽  
Hadi M. Yassine ◽  
...  

MicroRNA (miRNAs), a class of small, endogenous non-coding RNA molecules of about 21-24 nucleotides in length, have unraveled a new modulatory network of RNAs that form an additional level of posttranscriptional gene regulation by targeting messenger RNAs (mRNAs). These miRNAs possess the ability to regulate gene expression by modulating the stability of mRNAs, controlling their translation rates, and consequently regulating protein synthesis. Substantial experimental evidence established the involvement of miRNAs in most biological processes like growth, differentiation, development, and metabolism in mammals including humans. An aberrant expression of miRNAs has been implicated in several pathologies, including cancer. The association of miRNAs with tumor growth, development, and metastasis depicts their potential as effective diagnostic and prognostic biomarkers. Furthermore, exploitation of the role of different miRNAs as oncogenes or tumor suppressors has aided in designing several miRNA-based therapeutic approaches for treating cancer patients whose clinical trials are underway. In this review, we aim to summarize the biogenesis of miRNAs and the dysregulations in these pathways that result in various pathologies and in some cases, resistance to drug treatment. We provide a detailed review of the miRNA expression signatures in different cancers along with their diagnostic and prognostic utility. Furthermore, we elaborate on the potential employment of miRNAs to enhance cancer cell apoptosis, regress tumor progression and even overcome miRNA-induced drug resistance.


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