scholarly journals Selection against maternal microRNA target sites in maternal transcripts

2014 ◽  
Author(s):  
Antonio Marco
Keyword(s):  
Small Rnas ◽  
Early Embryo ◽  
Microrna Target ◽  
Protein Coding ◽  
Functional Impact ◽  
Rna Molecules ◽  
Target Sites ◽  
Maternal Transcripts ◽  
Gene Transcripts

In animals, before the zygotic genome is expressed, the egg already contains gene products deposited by the mother. These maternal products are crucial during the initial steps of development. In Drosophila melanogaster a large number of maternal products are found in the oocyte, some of which are indispensable. Many of these products are RNA molecules, such as gene transcripts and ribosomal RNAs. Recently, microRNAs ? small RNA gene regulators ? have been detected early during development and are important in these initial steps. The presence of some microRNAs in unfertilized eggs has been reported, but whether they have a functional impact in the egg or early embryo has not being explored. I have extracted and sequenced small RNAs from Drosophila unfertilized eggs. The unfertilized egg is rich in small RNAs and contains multiple microRNA products. Maternal microRNAs are often encoded within the intron of maternal genes, suggesting that many maternal microRNAs are the product of transcriptional hitch-hiking. Comparative genomics analyses suggest that maternal transcripts tend to avoid target sites for maternal microRNAs. I also developed a microRNA target mutation model to study the functional impact of polymorphisms at microRNA target sites. The analysis of Drosophila populations suggests that there is selection against maternal microRNA target sites in maternal transcripts. A potential role of the maternal microRNA mir-9c in maternal-to-zygotic transition is also discussed. In conclusion, maternal microRNAs in Drosophila have a functional impact in maternal protein-coding transcripts.

Bioinformatics Methods for Studying MicroRNA and ARE-Mediated Regulation of Post-Transcriptional Gene Expression

2010 ◽  
Vol 1 (3) ◽  
pp. 97-112 ◽  
Author(s):  
Richipal Singh Bindra ◽  
Jason T. L. Wang ◽  
Paramjeet Singh Bagga
Keyword(s):  
Mirna Target ◽  
Target Prediction ◽  
Untranslated Regions ◽  
Regulatory Rna ◽  
Rna Motifs ◽  
Protein Coding ◽  
Rna Molecules ◽  
Cellular Processes ◽  
Target Sites ◽  
Transcriptional Gene Regulation

MicroRNAs (miRNAs) are short single-stranded RNA molecules with 21-22 nucleotides known to regulate post-transcriptional expression of protein-coding genes involved in most of the cellular processes. Prediction of miRNA targets is a challenging bioinformatics problem. AU-rich elements (AREs) are regulatory RNA motifs found in the 3’ untranslated regions (UTRs) of mRNAs, and they play dominant roles in the regulated decay of short-lived human mRNAs via specific interactions with proteins. In this paper, the authors review several miRNA target prediction tools and data sources, as well as computational methods used for the prediction of AREs. The authors discuss the connection between miRNA and ARE-mediated post-transcriptional gene regulation. Finally, a data mining method for identifying the co-occurrences of miRNA target sites in ARE containing genes is presented.

scholarly journals Long-Noncoding RNA (lncRNA) in the Regulation of Hypoxia-Inducible Factor (HIF) in Cancer

2020 ◽  
Vol 6 (3) ◽  
pp. 27 ◽  
Author(s):  
Dominik A. Barth ◽  
Felix Prinz ◽  
Julia Teppan ◽  
Katharina Jonas ◽  
Christiane Klec ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Protein Coding ◽  
Rna Molecules ◽  
Von Hippel Lindau ◽  
Hypoxic Conditions ◽  
Main Regulator ◽  
Upstream Regulators

Hypoxia is dangerous for oxygen-dependent cells, therefore, physiological adaption to cellular hypoxic conditions is essential. The transcription factor hypoxia-inducible factor (HIF) is the main regulator of hypoxic metabolic adaption reducing oxygen consumption and is regulated by gradual von Hippel-Lindau (VHL)-dependent proteasomal degradation. Beyond physiology, hypoxia is frequently encountered within solid tumors and first drugs are in clinical trials to tackle this pathway in cancer. Besides hypoxia, cancer cells may promote HIF expression under normoxic conditions by altering various upstream regulators, cumulating in HIF upregulation and enhanced glycolysis and angiogenesis, altogether promoting tumor proliferation and progression. Therefore, understanding the underlying molecular mechanisms is crucial to discover potential future therapeutic targets to evolve cancer therapy. Long non-coding RNAs (lncRNA) are a class of non-protein coding RNA molecules with a length of over 200 nucleotides. They participate in cancer development and progression and might act as either oncogenic or tumor suppressive factors. Additionally, a growing body of evidence supports the role of lncRNAs in the hypoxic and normoxic regulation of HIF and its subunits HIF-1α and HIF-2α in cancer. This review provides a comprehensive update and overview of lncRNAs as regulators of HIFs expression and activation and discusses and highlights potential involved pathways.

scholarly journals Functions and Roles of Long-Non-Coding RNAs in Human Nasopharyngeal Carcinoma

2018 ◽  
Vol 45 (3) ◽  
pp. 1191-1204 ◽  
Author(s):  
JingJing Wu ◽  
Swei Sunny Hann
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Functional Characterization ◽  
Clinical Information ◽  
Stem Cell Differentiation ◽  
Cancer Prognosis ◽  
Protein Coding ◽  
Rna Molecules ◽  
Gene Therapies ◽  
Non Coding Rnas

Nasopharyngeal carcinoma (NPC) is one of the most common cancers originating in the nasopharynx and occurring at high frequency in South-eastern Asia and North Africa. Long non-coding RNAs (lncRNAs) are a class of non-protein-coding RNA molecules and key regulators of developmental, physiological, and pathological processes in humans. Emerging studies have shown that lncRNAs play critical roles in tumorgenicity and cancer prognosis. With the development of deep sequencing analyses, an extensive amount of functional lncRNAs have been discovered in nasopharyngeal carcinoma tissues and cell lines. However, the roles and mechanisms of aberrantly expressed lncRNAs in the pathogenesis of NPC are not fully understood. In this review, we briefly illustrate the concept, identification, functional characterization, and summarize recent advancements of biological functions of lncRNAs with heterogeneous mechanistic characterization and their involvement in NPC. Then, we describe individual lncRNAs that have been associated with tumorgenesis, growth, invasion, cancer stem cell differentiation, metastasis, drug resistance and discuss the strategies of their therapeutic manipulation in NPC. We also review the emerging insights into the role of lncRNAs and their potential as biomarkers and therapeutic targets for novel treatment paradigms. Finally, we highlight the up-to-date of clinical information involving lncRNAs and future directions in the linking lncRNAs to potential gene therapies, and how modifications of lncRNAs can be exploited for prevention and treatment of NPC.

scholarly journals Conserved Cu-MicroRNAs in Arabidopsis thaliana Function in Copper Economy under Deficiency

Plants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 141 ◽  
Author(s):  
Muhammad Shahbaz ◽  
Marinus Pilon
Keyword(s):  
Arabidopsis Thaliana ◽  
Small Rnas ◽  
Wild Type ◽  
Microrna Target ◽  
Electron Carrier ◽  
Cu Deficiency ◽  
Regulatory Circuits ◽  
Transgenic Lines ◽  
Cu Homeostasis

Copper (Cu) is a micronutrient for plants. Three small RNAs, which are up-regulated by Cu deficiency and target transcripts for Cu proteins, are among the most conserved microRNAs in plants. It was hypothesized that these Cu-microRNAs help save Cu for the most essential Cu-proteins under deficiency. Testing this hypothesis has been a challenge due to the redundancy of the Cu microRNAs and the properties of the regulatory circuits that control Cu homeostasis. In order to investigate the role of Cu-microRNAs in Cu homeostasis during vegetative growth, we used a tandem target mimicry strategy to simultaneously inhibit the function of three conserved Cu-microRNAs in Arabidopsis thaliana. When compared to wild-type, transgenic lines that express the tandem target mimicry construct showed reduced Cu-microRNA accumulation and increased accumulation of transcripts that encode Cu proteins. As a result, these mimicry lines showed impaired photosynthesis and growth compared to wild type on low Cu, which could be ascribed to a defect in accumulation of plastocyanin, a Cu-containing photosynthetic electron carrier, which is itself not a Cu-microRNA target. These data provide experimental support for a Cu economy model where the Cu-microRNAs together function to allow maturation of essential Cu proteins under impending deficiency.

scholarly journals Conservation and novelty in the microRNA genomic landscape of hyperdiverse cichlid fishes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Peiwen Xiong ◽  
Ralf F. Schneider ◽  
C. Darrin Hulsey ◽  
Axel Meyer ◽  
Paolo Franchini
Keyword(s):  
Messenger Rna ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Protein Coding ◽  
Adaptive Diversification ◽  
Cichlid Fishes ◽  
Novel Mirna ◽  
Genomic Landscape ◽  
Target Sites

Abstract MicroRNAs (miRNAs) play crucial roles in the post-transcriptional control of messenger RNA (mRNA). These miRNA-mRNA regulatory networks are present in nearly all organisms and contribute to development, phenotypic divergence, and speciation. To examine the miRNA landscape of cichlid fishes, one of the most species-rich families of vertebrates, we profiled the expression of both miRNA and mRNA in a diverse set of cichlid lineages. Among these, we found that conserved miRNAs differ from recently arisen miRNAs (i.e. lineage specific) in average expression levels, number of target sites, sequence variability, and physical clustering patterns in the genome. Furthermore, conserved miRNA target sites tend to be enriched at the 5′ end of protein-coding gene 3′ UTRs. Consistent with the presumed regulatory role of miRNAs, we detected more negative correlations between the expression of miRNA-mRNA functional pairs than in random pairings. Finally, we provide evidence that novel miRNA targets sites are enriched in genes involved in protein synthesis pathways. Our results show how conserved and evolutionarily novel miRNAs differ in their contribution to the genomic landscape and highlight their particular evolutionary roles in the adaptive diversification of cichlids.

Roles of the U5 snRNP in spliceosome dynamics and catalysis

2004 ◽  
Vol 32 (6) ◽  
pp. 928-931 ◽  
Author(s):  
I.A. Turner ◽  
C.M. Norman ◽  
M.J. Churcher ◽  
A.J. Newman
Keyword(s):  
Mrna Splicing ◽  
Small Nuclear Rna ◽  
Protein Coding ◽  
Rna Molecules ◽  
Small Nuclear Ribonucleoprotein ◽  
Associated Proteins ◽  
Gene Transcripts ◽  
Protein Components ◽  
Intron Removal ◽  
Nuclear Ribonucleoprotein

Most protein-coding genes in eukaryotes are interrupted by non-coding intervening sequences (introns), which must be precisely removed from primary gene transcripts (pre-mRNAs) before translation of the message into protein. Intron removal by pre-mRNA splicing occurs in the nucleus and is catalysed by complex ribonucleoprotein machines called spliceosomes. These molecular machines consist of several small nuclear RNA molecules and their associated proteins [together termed snRNP (small nuclear ribonucleoprotein) particles], plus multiple accessory factors. Of particular interest are the U2, U5 and U6 snRNPs, which play crucial roles in the catalytic steps of splicing. In the present review, we summarize our current understanding of the role played by the protein components of the U5 snRNP in pre-mRNA splicing, which include some of the largest and most highly conserved nuclear proteins.

scholarly journals Non-Coding RNA Databases in Cardiovascular Research

2020 ◽  
Vol 6 (3) ◽  
pp. 35
Author(s):  
Deepak Balamurali ◽  
Monika Stoll
Keyword(s):  
Vascular System ◽  
Cardiovascular Research ◽  
Data Repositories ◽  
Protein Coding ◽  
Rna Molecules ◽  
High Throughput Data ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Generation Sequencing

Cardiovascular diseases (CVDs) are of multifactorial origin and can be attributed to several genetic and environmental components. CVDs are the leading cause of mortality worldwide and they primarily damage the heart and the vascular system. Non-coding RNA (ncRNA) refers to functional RNA molecules, which have been transcribed into DNA but do not further get translated into proteins. Recent transcriptomic studies have identified the presence of thousands of ncRNA molecules across species. In humans, less than 2% of the total genome represents the protein-coding genes. While the role of many ncRNAs is yet to be ascertained, some long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been associated with disease progression, serving as useful diagnostic and prognostic biomarkers. A plethora of data repositories specialized in ncRNAs have been developed over the years using publicly available high-throughput data from next-generation sequencing and other approaches, that cover various facets of ncRNA research like basic and functional annotation, expressional profile, structural and molecular changes, and interaction with other biomolecules. Here, we provide a compendium of the current ncRNA databases relevant to cardiovascular research.

scholarly journals Role of MicroRNAs Induced by Chinese Herbal Medicines Against Hepatocellular Carcinoma: A Brief Review

2018 ◽  
Vol 17 (4) ◽  
pp. 1059-1067 ◽  
Author(s):  
Ge Guo ◽  
Juhua Zhou ◽  
Xiaogaung Yang ◽  
Jiang Feng ◽  
Yanxia Shao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Small Rnas ◽  
Herbal Medicines ◽  
Early Embryo ◽  
Invasion And Metastasis ◽  
Chinese Herbal Medicines ◽  
Regulate Gene Expression ◽  
Early Embryo Development ◽  
Chinese Herbal

MicroRNAs (miRNAs) are highly conserved, noncoding small RNAs that regulate gene expression, and consequently several important functions including early embryo development, cell cycle, programmed cell death, cell differentiation, and metabolism. While there are no effective treatments available against hepatocellular carcinoma (HCC), some Chinese herbal medicines have been shown to regulate growth, differentiation, invasion, and metastasis of HCC. Many studies have shown that Chinese herbal medicines regulate the expression of miRNAs and this may be associated with their ability to control the development of HCC. In this article, the effects of Chinese herbal medicines on the expression of miRNAs and their functions in the regulation of HCC have been reviewed and discussed. miRNAs such as miRNA-221 and miRNA-222 mediated by Chinese herbal medicines may be good biomarkers and therapeutic targets for HCC.

scholarly journals Roles for small noncoding RNAs in silencing of retrotransposons in the mammalian brain

2016 ◽  
Vol 113 (45) ◽  
pp. 12697-12702 ◽  
Author(s):  
Sayan Nandi ◽  
Dhruva Chandramohan ◽  
Luana Fioriti ◽  
Ari M. Melnick ◽  
Jean M. Hébert ◽  
...  
Keyword(s):  
Small Rnas ◽  
Large Scale ◽  
Regulation Of Gene Expression ◽  
Mammalian Brain ◽  
Long Term Memory ◽  
Protein Coding ◽  
Functional Roles ◽  
Small Noncoding Rnas ◽  
Single Base Pair

Piwi-interacting RNAs (piRNAs), long thought to be restricted to germline, have recently been discovered in neurons of Aplysia, with a role in the epigenetic regulation of gene expression underlying long-term memory. We here ask whether piwi/piRNAs are also expressed and have functional roles in the mammalian brain. Large-scale RNA sequencing and subsequent analysis of protein expression revealed the presence in brain of several piRNA biogenesis factors including a mouse piwi (Mili), as well as small RNAs, albeit at low levels, resembling conserved piRNAs in mouse testes [primarily LINE1 (long interspersed nuclear element1) retrotransposon-derived]. Despite the seeming low expression of these putative piRNAs, single-base pair CpG methylation analyses across the genome of Mili/piRNA-deficient (Mili−/−) mice demonstrate that brain genomic DNA is preferentially hypomethylated within intergenic areas and LINE1 promoter areas of the genome. Furthermore, Mili mutant mice exhibit behavioral deficits such as hyperactivity and reduced anxiety. These results suggest that putative piRNAs exist in mammalian brain, and similar to the role of piRNAs in testes, they may be involved in the silencing of retrotransposons, which in brain have critical roles in contributing to genomic heterogeneity underlying adaptation, stress response, and brain pathology. We also describe the presence of another class of small RNAs in the brain, with features of endogenous siRNAs, which may have taken over the role of invertebrate piRNAs in their capacity to target both transposons, as well as protein-coding genes. Thus, RNA interference through gene and retrotransposon silencing previously encountered in Aplysia may also have potential roles in the mammalian brain.

scholarly journals Compensatory sequence variation between trans-species small RNAs and their target sites

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Nathan R Johnson ◽  
Claude W dePamphilis ◽  
Michael J Axtell
Keyword(s):  
Small Rnas ◽  
Synonymous Site ◽  
Protein Coding ◽  
Coding Regions ◽  
Target Sites ◽  
Site Variation ◽  
Small Regulatory Rnas ◽  
Regulatory Rnas ◽  
Multiple Species ◽  
Multiple Variants

Trans-species small regulatory RNAs (sRNAs) are delivered to host plants from diverse pathogens and parasites and can target host mRNAs. How trans-species sRNAs can be effective on diverse hosts has been unclear. Multiple species of the parasitic plant Cuscuta produce trans-species sRNAs that collectively target many host mRNAs. Confirmed target sites are nearly always in highly conserved, protein-coding regions of host mRNAs. Cuscuta trans-species sRNAs can be grouped into superfamilies that have variation in a three-nucleotide period. These variants compensate for synonymous-site variation in host mRNAs. By targeting host mRNAs at highly conserved protein-coding sites, and simultaneously expressing multiple variants to cover synonymous-site variation, Cuscuta trans-species sRNAs may be able to successfully target multiple homologous mRNAs from diverse hosts.

Sign in / Sign up

Export Citation Format

Share Document