scholarly journals Exploring Evidence of Non-coding RNA Translation With Trips-Viz and GWIPS-Viz Browsers

Author(s):  
Oza Zaheed ◽  
Stephen J. Kiniry ◽  
Pavel V. Baranov ◽  
Kellie Dean

Detection of translation in so-called non-coding RNA provides an opportunity for identification of novel bioactive peptides and microproteins. The main methods used for these purposes are ribosome profiling and mass spectrometry. A number of publicly available datasets already exist for a substantial number of different cell types grown under various conditions, and public data mining is an attractive strategy for identification of translation in non-coding RNAs. Since the analysis of publicly available data requires intensive data processing, several data resources have been created recently for exploring processed publicly available data, such as OpenProt, GWIPS-viz, and Trips-Viz. In this work we provide a detailed demonstration of how to use the latter two tools for exploring experimental evidence for translation of RNAs hitherto classified as non-coding. For this purpose, we use a set of transcripts with substantially different patterns of ribosome footprint distributions. We discuss how certain features of these patterns can be used as evidence for or against genuine translation. During our analysis we concluded that the MTLN mRNA, previously misannotated as lncRNA LINC000116, likely encodes only a short proteoform expressed from shorter RNA transcript variants.

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 325
Author(s):  
Petra Korać ◽  
Mariastefania Antica ◽  
Maja Matulić

MicroRNAs (miRNAs) are short non-coding RNA involved in the regulation of specific mRNA translation. They participate in cellular signaling circuits and can act as oncogenes in tumor development, so-called oncomirs, as well as tumor suppressors. miR-7 is an ancient miRNA involved in the fine-tuning of several signaling pathways, acting mainly as tumor suppressor. Through downregulation of PI3K and MAPK pathways, its dominant role is the suppression of proliferation and survival, stimulation of apoptosis and inhibition of migration. Besides these functions, it has numerous additional roles in the differentiation process of different cell types, protection from stress and chromatin remodulation. One of the most investigated tissues is the brain, where its downregulation is linked with glioblastoma cell proliferation. Its deregulation is found also in other tumor types, such as in liver, lung and pancreas. In some types of lung and oral carcinoma, it can act as oncomir. miR-7 roles in cell fate determination and maintenance of cell homeostasis are still to be discovered, as well as the possibilities of its use as a specific biotherapeutic.


Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1711 ◽  
Author(s):  
Conor P. Duffy ◽  
Claire E. McCoy

Multiple sclerosis (MS) is an autoimmune disorder characterised by demyelination of central nervous system neurons with subsequent damage, cell death and disability. While mechanisms exist in the CNS to repair this damage, they are disrupted in MS and currently there are no treatments to address this deficit. In recent years, increasing attention has been paid to the influence of the small, non-coding RNA molecules, microRNAs (miRNAs), in autoimmune disorders, including MS. In this review, we examine the role of miRNAs in remyelination in the different cell types that contribute to MS. We focus on key miRNAs that have a central role in mediating the repair process, along with several more that play either secondary or inhibitory roles in one or more aspects. Finally, we consider the current state of miRNAs as therapeutic targets in MS, acknowledging current challenges and potential strategies to overcome them in developing effective novel therapeutics to enhance repair mechanisms in MS.


2018 ◽  
Vol 16 (02) ◽  
pp. 1840013 ◽  
Author(s):  
Oxana A. Volkova ◽  
Yury V. Kondrakhin ◽  
Timur A. Kashapov ◽  
Ruslan N. Sharipov

RNA plays an important role in the intracellular cell life and in the organism in general. Besides the well-established protein coding RNAs (messenger RNAs, mRNAs), long non-coding RNAs (lncRNAs) have gained the attention of recent researchers. Although lncRNAs have been classified as non-coding, some authors reported the presence of corresponding sequences in ribosome profiling data (Ribo-seq). Ribo-seq technology is a powerful experimental tool utilized to characterize RNA translation in cell with focus on initiation (harringtonine, lactimidomycin) and elongation (cycloheximide). By exploiting translation starts obtained from the Ribo-seq experiment, we developed a novel position weight matrix model for the prediction of translation starts. This model allowed us to achieve 96% accuracy of discrimination between human mRNAs and lncRNAs. When the same model was used for the prediction of putative ORFs in RNAs, we discovered that the majority of lncRNAs contained only small ORFs ([Formula: see text][Formula: see text]nt) in contrast to mRNAs.


Rheumatology ◽  
2019 ◽  
Vol 59 (1) ◽  
pp. 46-56 ◽  
Author(s):  
Yilong Fang ◽  
Jiajie Tu ◽  
Dafei Han ◽  
Yawei Guo ◽  
Wenming Hong ◽  
...  

Abstract RA is a chronic, autoimmune-mediated inflammatory pathology. Long non-coding RNAs (lncRNAs) are a novel group of non-coding RNAs with a length of >200 nucleotides. There are reports emerging that suggest that lncRNAs participate in establishing and sustaining autoimmune diseases, including RA. In this review article, we highlight the functions of lncRNAs in different cell types in RA. Our review indicates that lncRNAs affect various cellular components and are novel candidates that could constitute promising targets for the diagnosis and treatment of RA.


Author(s):  
Yanlei Yang ◽  
Suying Liu ◽  
Chengmei He ◽  
Zhilei Chen ◽  
Taibiao Lyu ◽  
...  

Given the self-renewal, multi-differentiation, immunoregulatory, and tissue maintenance properties, mesenchymal stem cells (MSCs) are promising candidates for stem cell-based therapies. Breakthroughs have been made in uncovering MSCs as key contributors to homeostasis and the regenerative repair of tissues and organs derived from three germ layers. MSC differentiation into specialized cell types is sophisticatedly regulated, and accumulating evidence suggests long non-coding RNAs (lncRNAs) as the master regulators of various biological processes including the maintenance of homeostasis and multi-differentiation functions through epigenetic, transcriptional, and post-translational mechanisms. LncRNAs are ubiquitous and generally referred to as non-coding transcripts longer than 200 bp. Most lncRNAs are evolutionary conserved and species-specific; however, the weak conservation of their sequences across species does not affect their diverse biological functions. Although numerous lncRNAs have been annotated and studied, they are nevertheless only the tip of the iceberg; the rest remain to be discovered. In this review, we characterize MSC functions in homeostasis and highlight recent advances on the functions and mechanisms of lncRNAs in regulating MSC homeostasis and differentiation. We also discuss the current challenges and perspectives for understanding the roles of lncRNAs in MSC functions in homeostasis, which could help develop promising targets for MSC-based therapies.


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Lavinia Raimondi ◽  
Angela De Luca ◽  
Eugenio Morelli ◽  
Gianluca Giavaresi ◽  
Pierosandro Tagliaferri ◽  
...  

Multiple myeloma (MM) is a hematologic malignancy of differentiated plasma cells that accumulate in the bone marrow, where a complex microenvironment made by different cell types supports proliferation, survival, and drug resistance of tumor cells. MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at posttranscriptional level. Emerging evidence indicates that miRNAs are aberrantly expressed or functionally deregulated in MM cells as the result of multiple genetic or epigenetic mechanisms and that also the tumor microenvironment regulates MM cell functions by miRNAs. Consistently, modulation of miRNA levels in MM cells has been demonstrated to impair their functional interaction with the bone marrow microenvironment and to produce significant antitumor activity even able to overcome the protective bone marrowmilieu. This review will describe the most recent findings on miRNA function in the context of MM bone marrow microenvironment, focusing on the therapeutic potential of miRNA-based approaches.


Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1576
Author(s):  
Jeffrey Solomon ◽  
Fabian Kern ◽  
Tobias Fehlmann ◽  
Eckart Meese ◽  
Andreas Keller

For many research aspects on small non-coding RNAs, especially microRNAs, computational tools and databases are developed. This includes quantification of miRNAs, piRNAs, tRNAs and tRNA fragments, circRNAs and others. Furthermore, the prediction of new miRNAs, isomiRs, arm switch events, target and target pathway prediction and miRNA pathway enrichment are common tasks. Additionally, databases and resources containing expression profiles, e.g., from different tissues, organs or cell types, are generated. This information in turn leads to improved miRNA repositories. While most of the respective tools are implemented in a species-independent manner, we focused on tools for human small non-coding RNAs. This includes four aspects: (1) miRNA analysis tools (2) databases on miRNAs and variations thereof (3) databases on expression profiles (4) miRNA helper tools facilitating frequent tasks such as naming conversion or reporter assay design. Although dependencies between the tools exist and several tools are jointly used in studies, the interoperability is limited. We present HumiR, a joint web presence for our tools. HumiR facilitates an entry in the world of miRNA research, supports the selection of the right tool for a research task and represents the very first step towards a fully integrated knowledge-base for human small non-coding RNA research. We demonstrate the utility of HumiR by performing a very comprehensive analysis of Alzheimer’s miRNAs.


2019 ◽  
Author(s):  
Wanassa Beroual ◽  
David Lalaouna ◽  
Nadia Ben Zaina ◽  
Odile Valette ◽  
Karine Prévost ◽  
...  

SummaryBacterial cells are powerful models for understanding how cells divide and accomplish global regulatory programs. In Caulobacter crescentus a cascade of essential master regulators regulate the correct and sequential activation of DNA replication, cell division and development of different cell types. Among them CtrA plays a crucial role coordinating all those functions. Despite decades of investigation, no control by non-coding RNAs (ncRNAs) has been linked to Caulobacter cell cycle. Here, for the first time we describe the role of a novel essential factor named CcnA, a ncRNA located at the origin of replication, activated by CtrA and responsible for the rapid and strong accumulation of CtrA itself. In addition CcnA is also responsible for the inhibition of GcrA translation by direct interaction with its UTR region. By a combination of probing experiments and mutagenesis, we propose a new mechanism by liberation (CtrA) or sequestration (GcrA) of the Ribosome Binding Site (RBS). CcnA role is conserved in other alphaproteobacterial species, such as Sinorhizobium meliloti, representing indeed a conserved and fundamental process regulating cell cycle in Rhizobiales and Caulobacterales.


2021 ◽  
Vol 11 ◽  
Author(s):  
Erminia Rubino ◽  
Melania Cruciani ◽  
Nicolas Tchitchek ◽  
Anna Le Tortorec ◽  
Antoine D. Rolland ◽  
...  

Ubiquitin-specific peptidase 18 (USP18) acts as gatekeeper of type I interferon (IFN) responses by binding to the IFN receptor subunit IFNAR2 and preventing activation of the downstream JAK/STAT pathway. In any given cell type, the level of USP18 is a key determinant of the output of IFN-stimulated transcripts. How the baseline level of USP18 is finely tuned in different cell types remains ill defined. Here, we identified microRNAs (miRNAs) that efficiently target USP18 through binding to the 3’untranslated region (3’UTR). Among these, three miRNAs are particularly enriched in circulating monocytes which exhibit low baseline USP18. Intriguingly, the USP18 3’UTR sequence is duplicated in human and chimpanzee genomes. In humans, four USP18 3’UTR copies were previously found to be embedded in long intergenic non-coding (linc) RNA genes residing in chr22q11.21 and known as FAM247A-D. Here, we further characterized their sequence and measured their expression profile in human tissues. Importantly, we describe an additional lincRNA bearing USP18 3’UTR (here linc-UR-B1) that is expressed only in testis. RNA-seq data analyses from testicular cell subsets revealed a positive correlation between linc-UR-B1 and USP18 expression in spermatocytes and spermatids. Overall, our findings uncover a set of miRNAs and lincRNAs, which may be part of a network evolved to fine-tune baseline USP18, particularly in cell types where IFN responsiveness needs to be tightly controlled.


2021 ◽  
Vol 12 ◽  
Author(s):  
Haishuang Tang ◽  
Zhangwei Zeng ◽  
Chenghao Shang ◽  
Qiang Li ◽  
Jianmin Liu

Atherosclerosis, characterized by atherosclerotic plaques, is a complex pathological process that involves different cell types and can be seen as a chronic inflammatory disease. In the advanced stage, the ruptured atherosclerotic plaque can induce deadly accidents including ischemic stroke and myocardial infarction. Epigenetics regulation, including DNA methylation, histone modification, and non-coding RNA modification. maintains cellular identity via affecting the cellular transcriptome. The epigenetic modification process, mediating by epigenetic enzymes, is dynamic under various stimuli, which can be reversely altered. Recently, numerous studies have evidenced the close relationship between atherosclerosis and epigenetic regulations in atherosclerosis, providing us with a novel perspective in researching mechanisms and finding novel therapeutic targets of this serious disease. Here, we critically review the recent discoveries between epigenetic regulation mechanisms in atherosclerosis.


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