Functional profiling of long intergenic non-coding RNAs in fission yeast

Eukaryotic genomes express numerous long intergenic non-coding RNAs (lincRNAs) that do not overlap any coding genes. Some lincRNAs function in various aspects of gene regulation, but it is not clear in general to what extent lincRNAs contribute to the information flow from genotype to phenotype. To explore this question, we systematically analysed cellular roles of lincRNAs in Schizosaccharomyces pombe. Using seamless CRISPR/Cas9-based genome editing, we deleted 141 lincRNA genes to broadly phenotype these mutants, together with 238 diverse coding-gene mutants for functional context. We applied high-throughput colony-based assays to determine mutant growth and viability in benign conditions and in response to 145 different nutrient, drug, and stress conditions. These analyses uncovered phenotypes for 47.5% of the lincRNAs and 96% of the protein-coding genes. For 110 lincRNA mutants, we also performed high-throughput microscopy and flow cytometry assays, linking 37% of these lincRNAs with cell-size and/or cell-cycle control. With all assays combined, we detected phenotypes for 84 (59.6%) of all lincRNA deletion mutants tested. For complementary functional inference, we analysed colony growth of strains ectopically overexpressing 113 lincRNA genes under 47 different conditions. Of these overexpression strains, 102 (90.3%) showed altered growth under certain conditions. Clustering analyses provided further functional clues and relationships for some of the lincRNAs. These rich phenomics datasets associate lincRNA mutants with hundreds of phenotypes, indicating that most of the lincRNAs analysed exert cellular functions in specific environmental or physiological contexts. This study provides groundwork to further dissect the roles of these lincRNAs in the relevant conditions.

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Comprehensive functional profiling of long non-coding RNAs through a novel pan-cancer integration approach and modular analysis of their protein-coding gene association networks

BMC Genomics ◽

10.1186/s12864-019-5850-7 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Kevin Walters ◽

Radmir Sarsenov ◽

Wen Siong Too ◽

Roseanna K. Hare ◽

Ian C. Paterson ◽

...

Keyword(s):

Protein Coding ◽

Gene Association ◽

Integration Approach ◽

Functional Profiling ◽

Modular Analysis ◽

Non Coding Rnas ◽

Pan Cancer

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Conserved Small Nucleotidic Elements at the Origin of Concerted piRNA Biogenesis from Genes and lncRNAs

Cells ◽

10.3390/cells9061491 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1491

Author(s):

Silke Jensen ◽

Emilie Brasset ◽

Elise Parey ◽

Hugues Roest Crollius ◽

Igor V. Sharakhov ◽

...

Keyword(s):

Regulatory Pathway ◽

Cellular Functions ◽

Germline Development ◽

Protein Coding ◽

Ping Pong ◽

Sequence Complementarity ◽

New Type ◽

Non Coding Rnas ◽

Pirna Pathway ◽

Genomic Repeats

PIWI-interacting RNAs (piRNAs) target transcripts by sequence complementarity serving as guides for RNA slicing in animal germ cells. The piRNA pathway is increasingly recognized as critical for essential cellular functions such as germline development and reproduction. In the Anopheles gambiae ovary, as much as 11% of piRNAs map to protein-coding genes. Here, we show that ovarian mRNAs and long non-coding RNAs (lncRNAs) are processed into piRNAs that can direct other transcripts into the piRNA biogenesis pathway. Targeting piRNAs fuel transcripts either into the ping-pong cycle of piRNA amplification or into the machinery of phased piRNA biogenesis, thereby creating networks of inter-regulating transcripts. RNAs of the same network share related genomic repeats. These repeats give rise to piRNAs, which target other transcripts and lead to a cascade of concerted RNA slicing. While ping-pong networks are based on repeats of several hundred nucleotides, networks that rely on phased piRNA biogenesis operate through short ~40-nucleotides long repeats, which we named snetDNAs. Interestingly, snetDNAs are recurring in evolution from insects to mammals. Our study brings to light a new type of conserved regulatory pathway, the snetDNA-pathway, by which short sequences can include independent genes and lncRNAs in the same biological pathway.

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The Role of LncRNAs in Translation

Non-Coding RNA ◽

10.3390/ncrna7010016 ◽

2021 ◽

Vol 7 (1) ◽

pp. 16

Author(s):

Didem Karakas ◽

Bulent Ozpolat

Keyword(s):

Transcriptional Activation ◽

Chromatin Modification ◽

Protein Translation ◽

Cellular Functions ◽

Protein Coding ◽

Regulate Gene Expression ◽

Translational Machinery ◽

Wide Range ◽

Non Coding Rnas

Long non-coding RNAs (lncRNAs), a group of non-protein coding RNAs with lengths of more than 200 nucleotides, exert their effects by binding to DNA, mRNA, microRNA, and proteins and regulate gene expression at the transcriptional, post-transcriptional, translational, and post-translational levels. Depending on cellular location, lncRNAs are involved in a wide range of cellular functions, including chromatin modification, transcriptional activation, transcriptional interference, scaffolding and regulation of translational machinery. This review highlights recent studies on lncRNAs in the regulation of protein translation by modulating the translational factors (i.e, eIF4E, eIF4G, eIF4A, 4E-BP1, eEF5A) and signaling pathways involved in this process as wells as their potential roles as tumor suppressors or tumor promoters.

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Non-Coding RNAs and their Integrated Networks

Journal of Integrative Bioinformatics ◽

10.1515/jib-2019-0027 ◽

2019 ◽

Vol 16 (3) ◽

Cited By ~ 16

Author(s):

Peijing Zhang ◽

Wenyi Wu ◽

Qi Chen ◽

Ming Chen

Keyword(s):

Gene Regulatory Networks ◽

Regulatory Networks ◽

Protein Coding ◽

Integrated Networks ◽

Cellular Processes ◽

Sequencing Technologies ◽

Different Types ◽

Gene Regulatory ◽

Non Coding Rnas ◽

Eukaryotic Genomes

AbstractEukaryotic genomes are pervasively transcribed. Besides protein-coding RNAs, there are different types of non-coding RNAs that modulate complex molecular and cellular processes. RNA sequencing technologies and bioinformatics methods greatly promoted the study of ncRNAs, which revealed ncRNAs’ essential roles in diverse aspects of biological functions. As important key players in gene regulatory networks, ncRNAs work with other biomolecules, including coding and non-coding RNAs, DNAs and proteins. In this review, we discuss the distinct types of ncRNAs, including housekeeping ncRNAs and regulatory ncRNAs, their versatile functions and interactions, transcription, translation, and modification. Moreover, we summarize the integrated networks of ncRNA interactions, providing a comprehensive landscape of ncRNAs regulatory roles.

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Role of Pseudogenes in Tumorigenesis

Cancers ◽

10.3390/cancers10080256 ◽

2018 ◽

Vol 10 (8) ◽

pp. 256 ◽

Cited By ~ 29

Author(s):

Xinling Hu ◽

Liu Yang ◽

Yin-Yuan Mo

Keyword(s):

Critical Role ◽

Cellular Functions ◽

Protein Coding ◽

Master Regulators ◽

Protein Coding Genes ◽

The Past ◽

High Sequence Homology ◽

Regulation Mechanisms ◽

Non Coding Rnas

Functional genomics has provided evidence that the human genome transcribes a large number of non-coding genes in addition to protein-coding genes, including microRNAs and long non-coding RNAs (lncRNAs). Among the group of lncRNAs are pseudogenes that have not been paid attention in the past, compared to other members of lncRNAs. However, increasing evidence points the important role of pseudogenes in diverse cellular functions, and dysregulation of pseudogenes are often associated with various human diseases including cancer. Like other types of lncRNAs, pseudogenes can also function as master regulators for gene expression and thus, they can play a critical role in various aspects of tumorigenesis. In this review we discuss the latest developments in pseudogene research, focusing on how pseudogenes impact tumorigenesis through different gene regulation mechanisms. Given the high sequence homology with the corresponding parent genes, we also discuss challenges for pseudogene research.

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The expanding regulatory universe of p53 in gastrointestinal cancer

F1000Research ◽

10.12688/f1000research.8363.1 ◽

2016 ◽

Vol 5 ◽

pp. 756 ◽

Cited By ~ 6

Author(s):

Andrew Fesler ◽

Ning Zhang ◽

Jingfang Ju

Keyword(s):

Gastrointestinal Cancer ◽

Regulatory Network ◽

Cancer Biology ◽

Control Cell ◽

Cellular Functions ◽

Protein Coding ◽

Growth Environment ◽

Damage Repair ◽

Non Coding Rnas ◽

And Function

Tumor suppresser geneTP53is one of the most frequently deleted or mutated genes in gastrointestinal cancers. As a transcription factor, p53 regulates a number of important protein coding genes to control cell cycle, cell death, DNA damage/repair, stemness, differentiation and other key cellular functions. In addition, p53 is also able to activate the expression of a number of small non-coding microRNAs (miRNAs) through direct binding to the promoter region of these miRNAs. Many miRNAs have been identified to be potential tumor suppressors by regulating key effecter target mRNAs. Our understanding of the regulatory network of p53 has recently expanded to include long non-coding RNAs (lncRNAs). Like miRNA, lncRNAs have been found to play important roles in cancer biology. With our increased understanding of the important functions of these non-coding RNAs and their relationship with p53, we are gaining exciting new insights into the biology and function of cells in response to various growth environment changes. In this review we summarize the current understanding of the ever expanding involvement of non-coding RNAs in the p53 regulatory network and its implications for our understanding of gastrointestinal cancer.

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Long non-coding RNAs and human disease

Biochemical Society Transactions ◽

10.1042/bst20120020 ◽

2012 ◽

Vol 40 (4) ◽

pp. 902-906 ◽

Cited By ~ 163

Author(s):

Lorna W. Harries

Keyword(s):

Human Disease ◽

Fine Tuning ◽

Protein Coding ◽

Cellular Processes ◽

Small Regulatory Rnas ◽

Non Coding Rnas ◽

Interfering Rna ◽

Coding Potential ◽

Eukaryotic Genomes

The central dogma of molecular biology states that DNA is transcribed into RNA, which in turn is translated into proteins. We now know, however, that as much as 50% of the transcriptome has no protein-coding potential, but rather represents an important class of regulatory molecules responsible for the fine-tuning of gene expression. Although the role of small regulatory RNAs [microRNAs and siRNAs (small interfering RNA)] is well defined, another much less characterized category of non-coding transcripts exists, namely lncRNAs (long non-coding RNAs). Pervasively expressed by eukaryotic genomes, lncRNAs can be kilobases long and regulate their targets by influencing the epigenetic control, chromatin status, mRNA processing or translation capacity of their targets. In the present review, I outline the potential mechanisms of action of lncRNAs, the cellular processes that have been associated with them, and also explore some of the emerging evidence for their involvement in common human disease.

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The Role of microRNAs in the Viral Infections

Current Pharmaceutical Design ◽

10.2174/1381612825666190110161034 ◽

2019 ◽

Vol 24 (39) ◽

pp. 4659-4667 ◽

Cited By ~ 4

Author(s):

Mona Fani ◽

Milad Zandi ◽

Majid Rezayi ◽

Nastaran Khodadad ◽

Hadis Langari ◽

...

Keyword(s):

Viral Infections ◽

Rna Viruses ◽

Regulation Of Gene Expression ◽

Molecular Structures ◽

Main Function ◽

Cellular Functions ◽

Viral Genes ◽

Non Coding Rnas ◽

Post Transcriptional Regulation

MicroRNAs (miRNAs) are non-coding RNAs with 19 to 24 nucleotides which are evolutionally conserved. MicroRNAs play a regulatory role in many cellular functions such as immune mechanisms, apoptosis, and tumorigenesis. The main function of miRNAs is the post-transcriptional regulation of gene expression via mRNA degradation or inhibition of translation. In fact, many of them act as an oncogene or tumor suppressor. These molecular structures participate in many physiological and pathological processes of the cell. The virus can also produce them for developing its pathogenic processes. It was initially thought that viruses without nuclear replication cycle such as Poxviridae and RNA viruses can not code miRNA, but recently, it has been proven that RNA viruses can also produce miRNA. The aim of this articles is to describe viral miRNAs biogenesis and their effects on cellular and viral genes.

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Investigation of long non-coding RNAs as regulatory players of grapevine response to powdery and downy mildew infection

BMC Plant Biology ◽

10.1186/s12870-021-03059-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Garima Bhatia ◽

Santosh K. Upadhyay ◽

Anuradha Upadhyay ◽

Kashmir Singh

Keyword(s):

Downy Mildew ◽

Plasmopara Viticola ◽

Defense Responses ◽

Protein Coding ◽

Functional Roles ◽

Real Time Quantitative Pcr ◽

Transcriptional Reprogramming ◽

Sequencing Technologies ◽

Non Coding Rnas ◽

Fungal Phytopathogens

Abstract Background Long non-coding RNAs (lncRNAs) are regulatory transcripts of length > 200 nt. Owing to the rapidly progressing RNA-sequencing technologies, lncRNAs are emerging as considerable nodes in the plant antifungal defense networks. Therefore, we investigated their role in Vitis vinifera (grapevine) in response to obligate biotrophic fungal phytopathogens, Erysiphe necator (powdery mildew, PM) and Plasmopara viticola (downy mildew, DM), which impose huge agro-economic burden on grape-growers worldwide. Results Using computational approach based on RNA-seq data, 71 PM- and 83 DM-responsive V. vinifera lncRNAs were identified and comprehensively examined for their putative functional roles in plant defense response. V. vinifera protein coding sequences (CDS) were also profiled based on expression levels, and 1037 PM-responsive and 670 DM-responsive CDS were identified. Next, co-expression analysis-based functional annotation revealed their association with gene ontology (GO) terms for ‘response to stress’, ‘response to biotic stimulus’, ‘immune system process’, etc. Further investigation based on analysis of domains, enzyme classification, pathways enrichment, transcription factors (TFs), interactions with microRNAs (miRNAs), and real-time quantitative PCR of lncRNAs and co-expressing CDS pairs suggested their involvement in modulation of basal and specific defense responses such as: Ca2+-dependent signaling, cell wall reinforcement, reactive oxygen species metabolism, pathogenesis related proteins accumulation, phytohormonal signal transduction, and secondary metabolism. Conclusions Overall, the identified lncRNAs provide insights into the underlying intricacy of grapevine transcriptional reprogramming/post-transcriptional regulation to delay or seize the living cell-dependent pathogen growth. Therefore, in addition to defense-responsive genes such as TFs, the identified lncRNAs can be further examined and leveraged to candidates for biotechnological improvement/breeding to enhance fungal stress resistance in this susceptible fruit crop of economic and nutritional importance.

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