DOCSLIB.ORG

Mechanisms and Functions of Long Non-Coding Rnas at Multiple Regulatory Levels

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mechanisms and Functions of Long Non-Coding Rnas at Multiple Regulatory Levels International Journal of Molecular Sciences Review Mechanisms and Functions of Long Non-Coding RNAs at Multiple Regulatory Levels Xiaopei Zhang 1, Wei Wang 1 , Weidong Zhu 2, Jie Dong 1, Yingying Cheng 1, Zujun Yin 2,* and Fafu Shen 1,* 1 State Key Laboratory of Crop Biology, College of Agronomy, Shandong Agricultural University, NO. 61 Daizong Street, Tai’an 271018, Shandong, China; [email protected] (X.Z.); [email protected] (W.W.); [email protected] (J.D.); [email protected] (Y.C.) 2 State Key Laboratory of Cotton Biology, Chinese Academy of Agricultural Sciences Cotton Research Institute, Key Laboratory for Cotton Genetic Improvement, Anyang 45500, Henan, China; [email protected] * Correspondence: [email protected] (Z.Y.); [email protected] (F.S.); Tel.: +86-372-256-2219 (Z.Y.); +86-538-824-6011 (F.S.); Fax: +86-372-256-2311 (Z.Y.); +86-538-824-2226 (F.S.) Received: 20 September 2019; Accepted: 6 November 2019; Published: 8 November 2019 Abstract: Long non-coding (lnc) RNAs are non-coding RNAs longer than 200 nt. lncRNAs primarily interact with mRNA, DNA, protein, and miRNA and consequently regulate gene expression at the epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels in a variety of ways. They play important roles in biological processes such as chromatin remodeling, transcriptional activation, transcriptional interference, RNA processing, and mRNA translation. lncRNAs have important functions in plant growth and development; biotic and abiotic stress responses; and in regulation of cell differentiation, the cell cycle, and the occurrence of many diseases in humans and animals. In this review, we summarize the functions and mechanisms of lncRNAs in plants, humans, and animals at different regulatory levels. Keywords: lncRNA; epigenetic; transcriptional; post-transcriptional; translation; post-translational modification 1. Introduction Long non-coding (lnc) RNA transcripts are longer than 200 nt in length and have no protein-coding ability; however, they may have short open reading frames (ORFs). Most annotated lncRNAs are RNA polymerase II (Pol II) transcribed; hence, they are similar in structure to mRNA and may have cap structures and poly A tails. In addition, the plant-specific RNA polymerases, Pol IV and V, can produce lncRNAs [1,2]. LncRNAs comprise a diversified class of long intergenic non-coding (linc)-RNAs, long non-coding antisense transcripts, long intronic non-coding RNAs, and non-overlapping antisense lncRNAs [3]. LncRNA expression levels are lower than those of mRNA, and their sequence conservation is poor. For these reasons, few studies have been conducted on lncRNAs in plants, and this field remains in its infancy. In recent years, with the rapid development of biotechnology, many lncRNAs have been identified in animals and plants through microarrays, tiling arrays, expressed sequence tags (ESTs), and RNA-Seq. Many animal lncRNA biological functions have been confirmed; however, the biological functions of only a few plant lncRNAs have been studied [4,5]. Studies have indicated that lncRNAs are involved in epigenetic, transcriptional, post-transcriptional, and translation regulation, as well as post-translational modification [6–8]. LncRNAs have various regulatory functions in humans and animals. The main regulatory roles at the chromatin level are dosage compensation effects, genomic imprinting, chromatin modification, and remodeling [9–11]. LncRNAs also participate in regulating alternative splicing, cell differentiation, and cell cycle regulation, and they are involved in Int. J. Mol. Sci. 2019, 20, 5573; doi:10.3390/ijms20225573 www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2019, 20, 5573 2 of 29 Int. J. Mol. Sci. 2019, 20, x 2 of 28 regulating the occurrence of many diseases [12–15]. Plant lncRNAs play key roles in flowering time, rootregulation, organogenesis, and they seedling are involved photomorphogenesis, in regulating the sexual occurrence re-production, of many crop diseases yield, and[12–15]. responses Plant to bioticlncRNAs and abiotic play key stresses roles in [16 flowering–19]. time, root organogenesis, seedling photomorphogenesis, sexual re-production,According to crop the yield, current and understanding responses to biotic of lncRNA and abiotic identification stresses [16–19]. and function, these transcripts are broadlyAccording classified to the into current those understanding mediating chromatin of lncRNA modifications identification and and DNAfunction, methylation these transcripts involved inare epigenetic broadly regulation,classified into proteins those mediating (primarily chro transcriptionmatin modifications factor) and and DNA DNA interactions methylation involvedinvolved in transcriptionalin epigenetic regulation, level regulation, proteins and (primarily in mRNA tran processingscription factor) at the and post-transcriptional DNA interactions involved level, as in well astranscriptional direct interactions level withregulation, proteins and to in regulate mRNA proteinprocessing translation at the post-transcriptional and post-translation level, modification as well as (Figuredirect1 ).interactions In this review, with we proteins discuss to the regulate biological protein functions translation and regulatory and post-translation mechanisms modification of some plant (Figure 1). In this review, we discuss the biological functions and regulatory mechanisms of some and human lncRNAs. plant and human lncRNAs. FigureFigure 1. 1. RegulatoryRegulatory mechanisms mechanisms of lncR ofNAs lncRNAs at the genome at the level. genome (A) lncRNAs level. (interactA) lncRNAs with histone- interact withmodifying histone-modifying enzymes to activate enzymes or torepress activate gene or transcription. repress gene (B) transcription. lncRNAs recruit (B histone-modified) lncRNAs recruit histone-modifiedcomplexes or act complexesas scaffolds orforact multiple as sca histoneffolds formodifiers multiple to regulate histone histone modifiers modification to regulate of genes histone modificationand thereby of regulate genes andgene thereby transcription. regulate (C gene) lncRNAs transcription. recruit DNA (C) methyltransferases lncRNAs recruit DNAor methyltransferasesdemethylases to regulate or demethylases the target gene to regulate transcription. the target (D) genePol IV/V transcription. transcribed ( lncRNAsD) Pol IV are/V transcribedinvolved lncRNAsin RNA-dependent are involved DNA in methylation, RNA-dependent thus acti DNAvating methylation, or repressing thus gene activating transcription. or repressing(E,F) lncRNAs gene interact with transcription factors to activate or repress gene expression. (G) lncRNAs interact with transcription. (E,F) lncRNAs interact with transcription factors to activate or repress gene expression. splicing factors or proteins to regulate the mRNA alternative splicing; splicing factors directly (G) lncRNAs interact with splicing factors or proteins to regulate the mRNA alternative splicing; regulate the lncRNA’s alternative splicing in speckles. (H) lncRNAs act as miRNA sponges that splicing factors directly regulate the lncRNA’s alternative splicing in speckles. (H) lncRNAs act as regulate target gene expression. (I) lncRNAs act as miRNA or small interfering RNAs (siRNA) miRNA sponges that regulate target gene expression. (I) lncRNAs act as miRNA or small interfering precursors. (J) miRNAs target lncRNAs to produce siRNA or phased small-interfering RNAs RNAs (siRNA) precursors. (J) miRNAs target lncRNAs to produce siRNA or phased small-interfering (phasiRNAs). (K) lncRNAs are involved in the Staufen1-mediated mRNA decay, and lncRNAs bind RNAs (phasiRNAs). (K) lncRNAs are involved in the Staufen1-mediated mRNA decay, and lncRNAs to proteins and mediate mRNA decay. (L) lncRNAs directly bind to mRNA and regulate mRNA bind to proteins and mediate mRNA decay. (L) lncRNAs directly bind to mRNA and regulate mRNA stability, or competitively bind to mRNA to improve mRNA stability. (M) lncRNAs can be translated stability, or competitively bind to mRNA to improve mRNA stability. (M) lncRNAs can be translated to peptides. (N) lncRNAs interact with RNA methyltransferases or demethylases and thus regulate tomRNA peptides. expression. (N) lncRNAs (O) lncRNAs interact combine with RNA with methyltransferases proteins to regulate or protein demethylases localization. and (P thus) lncRNAs regulate mRNAinteract expression. with mRNAs (O) lncRNAsand affect combine mRNA withtranslation. proteins (Q to) regulatelncRNAs protein bind the localization. translation ( Pinitiation) lncRNAs interactcomplex with eIF mRNAs (eukaryotic and a initiationffect mRNA factor) translation. to regulate (Q) mRNA lncRNAs translation. bind the translation(R) lncRNAs initiation interact complex with eIFproteins (eukaryotic and control initiation protein factor) phosph to regulateorylation, mRNA acetylation, translation. and (ubiquiR) lncRNAstination interact at the post-translation with proteins and controllevel. protein phosphorylation, acetylation, and ubiquitination at the post-translation level. Int. J. Mol. Sci. 2019, 20, 5573 3 of 29 2. lncRNAs Are Involved in Regulating Histone Modifications at the Chromatin Level Epigenetics refers to heritable alterations in gene expression without alterations in DNA sequence. The molecular mechanisms involved primarily include DNA methylation, histone modification, chromatin remodeling, and, in a broad sense, non-coding RNA. Histone modifications are a major class of chromatin modifications responsible for the
Load more

Recommended publications
  • Spatially Heterogeneous Choroid Plexus Transcriptomes Encode Positional Identity and Contribute to Regional CSF Production
    The Journal of Neuroscience, March 25, 2015 • 35(12):4903–4916 • 4903 Development/Plasticity/Repair Spatially Heterogeneous Choroid Plexus Transcriptomes Encode Positional Identity and Contribute to Regional CSF Production Melody P. Lun,1,3 XMatthew B. Johnson,2 Kevin G. Broadbelt,1 Momoko Watanabe,4 Young-jin Kang,4 Kevin F. Chau,1 Mark W. Springel,1 Alexandra Malesz,1 Andre´ M.M. Sousa,5 XMihovil Pletikos,5 XTais Adelita,1,6 Monica L. Calicchio,1 Yong Zhang,7 Michael J. Holtzman,7 Hart G.W. Lidov,1 XNenad Sestan,5 Hanno Steen,1 XEdwin S. Monuki,4 and Maria K. Lehtinen1 1Department of Pathology, and 2Division of Genetics, Boston Children’s Hospital, Boston, Massachusetts 02115, 3Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, 4Department of Pathology and Laboratory Medicine, University of California Irvine School of Medicine, Irvine, California 92697, 5Department of Neurobiology and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510, 6Department of Biochemistry, Federal University of Sa˜o Paulo, Sa˜o Paulo 04039, Brazil, and 7Pulmonary and Critical Care Medicine, Department of Medicine, Washington University, St Louis, Missouri 63110 A sheet of choroid plexus epithelial cells extends into each cerebral ventricle and secretes signaling factors into the CSF. To evaluate whether differences in the CSF proteome across ventricles arise, in part, from regional differences in choroid plexus gene expression, we defined the transcriptome of lateral ventricle (telencephalic) versus fourth ventricle (hindbrain) choroid plexus. We find that positional identitiesofmouse,macaque,andhumanchoroidplexiderivefromgeneexpressiondomainsthatparalleltheiraxialtissuesoforigin.We thenshowthatmolecularheterogeneitybetweentelencephalicandhindbrainchoroidplexicontributestoregion-specific,age-dependent protein secretion in vitro.
    [Show full text]
  • Dna Methylation Post Transcriptional Modification
    Dna Methylation Post Transcriptional Modification Blistery Benny backbiting her tug-of-war so protectively that Scot barrel very weekends. Solanaceous and unpossessing Eric pubes her creatorships abrogating while Raymundo bereave some limitations demonstrably. Clair compresses his catchings getter epexegetically or epidemically after Bernie vitriols and piffling unchangeably, hypognathous and nourishing. To explore quantitative and dynamic properties of transcriptional regulation by. MeSH Cochrane Library. In revere last check of man series but left house with various gene expression profile of the effect of. Moreover interpretation of transcriptional changes during COVID-19 has been. In transcriptional modification by post transcriptional repression and posted by selective breeding industry: patterns of dna methylation during gc cells and the study of dna. DNA methylation regulates transcriptional homeostasis of. Be local in two ways Post Translational Modifications of amino acid residues of histone. International journal of cyclic gmp in a chromatin dynamics: unexpected results in alternative splicing of reusing and diagnosis of dmrs has been identified using whole process. Dam in dna methylation to violent outbursts that have originated anywhere in england and post transcriptional gene is regulated at the content in dna methylation post transcriptional modification of. A seven sample which customers post being the dtc company for analysis. Fei zhao y, methylation dynamics and modifications on lysine is an essential that. Tag-based our Generation Sequencing. DNA methylation and histone modifications as epigenetic. Thc content of. Lysine methylation has been involved in both transcriptional activation H3K4. For instance aberrance of DNA methylation andor demethylation has been. Chromosome conformation capture from 3C to 5C and will ChIP-based modification.
    [Show full text]
  • Translational Regulation During Oogenesis and Early Development: the Cap-Poly(A) Tail Relationship
    C. R. Biologies 328 (2005) 863–881 http://france.elsevier.com/direct/CRASS3/ Review / Revue Translational regulation during oogenesis and early development: The cap-poly(A) tail relationship Federica Piccioni a, Vincenzo Zappavigna b, Arturo C. Verrotti a,c,∗ a CEINGE–Biotecnologie Avanzate, Via Comunale Margherita 482, 80145 Napoli, Italy b Dipartimento di Biologia Animale, Università di Modena e Reggio Emilia, Via G. Campi 213d, 41100 Modena, Italy c Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli “Federico II”, Via S. Pansini 5, 80131 Napoli, Italy Received 27 February 2005; accepted after revision 10 May 2005 Available online 8 June 2005 Presented by Stuart Edelstein Abstract Metazoans rely on the regulated translation of select maternal mRNAs to control oocyte maturation and the initial stages of embryogenesis. These transcripts usually remain silent until their translation is temporally and spatially required during early development. Different translational regulatory mechanisms, varying from cytoplasmic polyadenylation to localization of maternal mRNAs, have evolved to assure coordinated initiation of development. A common feature of these mechanisms is that they share a few key trans-acting factors. Increasing evidence suggest that ubiquitous conserved mRNA-binding factors, including the eukaryotic translation initiation factor 4E (eIF4E) and the cytoplasmic polyadenylation element binding protein (CPEB), interact with cell-specific molecules to accomplish the correct level of translational activity necessary for normal development. Here we review how capping and polyadenylation of mRNAs modulate interaction with multiple regulatory factors, thus controlling translation during oogenesis and early development. To cite this article: F. Piccioni et al., C. R. Biologies 328 (2005). 2005 Académie des sciences.
    [Show full text]
  • Modes of Interaction of KMT2 Histone H3 Lysine 4 Methyltransferase/COMPASS Complexes with Chromatin
    cells Review Modes of Interaction of KMT2 Histone H3 Lysine 4 Methyltransferase/COMPASS Complexes with Chromatin Agnieszka Bochy ´nska,Juliane Lüscher-Firzlaff and Bernhard Lüscher * ID Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, Pauwelsstrasse 30, 52057 Aachen, Germany; [email protected] (A.B.); jluescher-fi[email protected] (J.L.-F.) * Correspondence: [email protected]; Tel.: +49-241-8088850; Fax: +49-241-8082427 Received: 18 January 2018; Accepted: 27 February 2018; Published: 2 March 2018 Abstract: Regulation of gene expression is achieved by sequence-specific transcriptional regulators, which convey the information that is contained in the sequence of DNA into RNA polymerase activity. This is achieved by the recruitment of transcriptional co-factors. One of the consequences of co-factor recruitment is the control of specific properties of nucleosomes, the basic units of chromatin, and their protein components, the core histones. The main principles are to regulate the position and the characteristics of nucleosomes. The latter includes modulating the composition of core histones and their variants that are integrated into nucleosomes, and the post-translational modification of these histones referred to as histone marks. One of these marks is the methylation of lysine 4 of the core histone H3 (H3K4). While mono-methylation of H3K4 (H3K4me1) is located preferentially at active enhancers, tri-methylation (H3K4me3) is a mark found at open and potentially active promoters. Thus, H3K4 methylation is typically associated with gene transcription. The class 2 lysine methyltransferases (KMTs) are the main enzymes that methylate H3K4. KMT2 enzymes function in complexes that contain a necessary core complex composed of WDR5, RBBP5, ASH2L, and DPY30, the so-called WRAD complex.
    [Show full text]
  • Mechanism of Lncrna FEZF1-AS1 in Promoting the Occurrence and Development of Oral Squamous Cell Carcinoma Through Targeting Mir-196A
    European Review for Medical and Pharmacological Sciences 2019; 23: 6505-6515 Mechanism of lncRNA FEZF1-AS1 in promoting the occurrence and development of oral squamous cell carcinoma through targeting miR-196a L. XU, T.-J. HOU, P. YANG Department of Stomatology, Liaocheng People’s Hospital, Liaocheng, China Lin Xu and Tiejun Hou contributed equally to this work Abstract. – OBJECTIVE: Previous studies have Meanwhile, the miR-196a expression was nega- demonstrated that long non-coding ribonucleic tively correlated with FEZF1-AS1. Subsequent acid (lncRNA) FEZF1-AS1 acts as a cancer-pro- Luciferase reporter gene assay confirmed that moting gene. However, no reports have investi- overexpression of miR-196a could markedly re- gated the role of FEZF1-AS1 in oral squamous cell duce the activity of Luciferase containing wild- carcinoma (OSCC) yet. Therefore, the aim of this type FEZF1-AS1 vector rather than decrease the study was to explore whether FEZF1-AS1 promot- activity of Luciferase containing mutant-type ed the expression characteristics of OSCC by tar- vector or empty vector. These findings further geting miR-196a and to further elucidate the un- indicated that FEZF1-AS1 could be targeted by derlying mechanism of FEZF1-AS1 in promoting miR-196a through this binding site. In addition, the metastasis of OSCC. recovery assay demonstrates that there was a PATIENTS AND METHODS: The expression mutual regulatory effect between FEZF1-AS1 levels of FEZF1-AS1 and miR-196a in 42 pairs of and miR-196a, jointly affecting the malignant OSCC tissues and para-carcinoma tissues were progression of OSCC. detected via quantitative Real Time-Polymerase CONCLUSIONS: The expression of lncRNA Chain Reaction (qRT-PCR).
    [Show full text]
  • A Long Noncoding RNA Maintains Active Chromatin to Coordinate Homeotic Gene Expression
    LETTER doi:10.1038/nature09819 A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression Kevin C. Wang1,2, Yul W. Yang1*, Bo Liu3*, Amartya Sanyal4, Ryan Corces-Zimmerman1, Yong Chen5, Bryan R. Lajoie4, Angeline Protacio1, Ryan A. Flynn1, Rajnish A. Gupta1, Joanna Wysocka6, Ming Lei5, Job Dekker4, Jill A. Helms3 & Howard Y. Chang1 The genome is extensively transcribed into long intergenic non- we suggest the name HOTTIP for ‘HOXA transcript at the distal tip’, coding RNAs (lincRNAs), many of which are implicated in gene exhibits bivalent H3K4me3 and H3K27me3, a histone modification silencing1,2. Potential roles of lincRNAs in gene activation are pattern associated with poised regulatory sequences16. Comparison much less understood3–5. Development and homeostasis require with RNA polymerase II occupancy and RNA expression showed that coordinate regulation of neighbouring genes through a process the bivalent H3K4me3 and H3K27me3 modifications on HOTTIP gene termed locus control6. Some locus control elements and enhancers do not require HOTTIP transcription, but transcription of HOTTIP is transcribe lincRNAs7–10, hinting at possible roles in long-range associated with increased H3K4me3 and decreased H3K27me3 (Fig. 1a, control. In vertebrates, 39 Hox genes, encoding homeodomain left). Chromatin immunoprecipitation (ChIP) analysis confirmed that transcription factors critical for positional identity, are clustered the HOTTIP gene is occupied by both polycomb repressive complex 2 in four chromosomal loci; the Hox genes are expressed in nested (PRC2) and MLL complex, consistent with the bivalent histone marks anterior-posterior and proximal-distal patterns colinear with their (Supplementary Fig. 1a). genomic position from 39 to 59of the cluster11.
    [Show full text]
  • Epigenetic Mechanisms of Lncrnas Binding to Protein in Carcinogenesis
    cancers Review Epigenetic Mechanisms of LncRNAs Binding to Protein in Carcinogenesis Tae-Jin Shin, Kang-Hoon Lee and Je-Yoel Cho * Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul 08826, Korea; [email protected] (T.-J.S.); [email protected] (K.-H.L.) * Correspondence: [email protected]; Tel.: +82-02-800-1268 Received: 21 September 2020; Accepted: 9 October 2020; Published: 11 October 2020 Simple Summary: The functional analysis of lncRNA, which has recently been investigated in various fields of biological research, is critical to understanding the delicate control of cells and the occurrence of diseases. The interaction between proteins and lncRNA, which has been found to be a major mechanism, has been reported to play an important role in cancer development and progress. This review thus organized the lncRNAs and related proteins involved in the cancer process, from carcinogenesis to metastasis and resistance to chemotherapy, to better understand cancer and to further develop new treatments for it. This will provide a new perspective on clinical cancer diagnosis, prognosis, and treatment. Abstract: Epigenetic dysregulation is an important feature for cancer initiation and progression. Long non-coding RNAs (lncRNAs) are transcripts that stably present as RNA forms with no translated protein and have lengths larger than 200 nucleotides. LncRNA can epigenetically regulate either oncogenes or tumor suppressor genes. Nowadays, the combined research of lncRNA plus protein analysis is gaining more attention. LncRNA controls gene expression directly by binding to transcription factors of target genes and indirectly by complexing with other proteins to bind to target proteins and cause protein degradation, reduced protein stability, or interference with the binding of other proteins.
    [Show full text]
  • Aberrant Activity of Histone–Lysine N-Methyltransferase 2 (KMT2) Complexes in Oncogenesis
    International Journal of Molecular Sciences Review Aberrant Activity of Histone–Lysine N-Methyltransferase 2 (KMT2) Complexes in Oncogenesis Elzbieta Poreba 1,* , Krzysztof Lesniewicz 2 and Julia Durzynska 1,* 1 Institute of Experimental Biology, Faculty of Biology, Adam Mickiewicz University, ul. Uniwersytetu Pozna´nskiego6, 61-614 Pozna´n,Poland 2 Department of Molecular and Cellular Biology, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, ul. Uniwersytetu Pozna´nskiego6, 61-614 Pozna´n,Poland; [email protected] * Correspondence: [email protected] (E.P.); [email protected] (J.D.); Tel.: +48-61-829-5857 (E.P.) Received: 19 November 2020; Accepted: 6 December 2020; Published: 8 December 2020 Abstract: KMT2 (histone-lysine N-methyltransferase subclass 2) complexes methylate lysine 4 on the histone H3 tail at gene promoters and gene enhancers and, thus, control the process of gene transcription. These complexes not only play an essential role in normal development but have also been described as involved in the aberrant growth of tissues. KMT2 mutations resulting from the rearrangements of the KMT2A (MLL1) gene at 11q23 are associated with pediatric mixed-lineage leukemias, and recent studies demonstrate that KMT2 genes are frequently mutated in many types of human cancers. Moreover, other components of the KMT2 complexes have been reported to contribute to oncogenesis. This review summarizes the recent advances in our knowledge of the role of KMT2 complexes in cell transformation. In addition, it discusses the therapeutic targeting of different components of the KMT2 complexes. Keywords: histone–lysine N-methyltransferase 2; COMPASS; COMPASS-like; H3K4 methylation; oncogenesis; cancer; epigenetics; chromatin 1.
    [Show full text]
  • How Influenza Virus Uses Host Cell Pathways During Uncoating
    cells Review How Influenza Virus Uses Host Cell Pathways during Uncoating Etori Aguiar Moreira 1 , Yohei Yamauchi 2 and Patrick Matthias 1,3,* 1 Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; [email protected] 2 Faculty of Life Sciences, School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK; [email protected] 3 Faculty of Sciences, University of Basel, 4031 Basel, Switzerland * Correspondence: [email protected] Abstract: Influenza is a zoonotic respiratory disease of major public health interest due to its pan- demic potential, and a threat to animals and the human population. The influenza A virus genome consists of eight single-stranded RNA segments sequestered within a protein capsid and a lipid bilayer envelope. During host cell entry, cellular cues contribute to viral conformational changes that promote critical events such as fusion with late endosomes, capsid uncoating and viral genome release into the cytosol. In this focused review, we concisely describe the virus infection cycle and highlight the recent findings of host cell pathways and cytosolic proteins that assist influenza uncoating during host cell entry. Keywords: influenza; capsid uncoating; HDAC6; ubiquitin; EPS8; TNPO1; pandemic; M1; virus– host interaction Citation: Moreira, E.A.; Yamauchi, Y.; Matthias, P. How Influenza Virus Uses Host Cell Pathways during 1. Introduction Uncoating. Cells 2021, 10, 1722. Viruses are microscopic parasites that, unable to self-replicate, subvert a host cell https://doi.org/10.3390/ for their replication and propagation. Despite their apparent simplicity, they can cause cells10071722 severe diseases and even pose pandemic threats [1–3].
    [Show full text]
  • Transcription Factors from Multiple Families Ensure Enhancer Selectivity
    bioRxiv preprint doi: https://doi.org/10.1101/2020.09.04.283036; this version posted September 4, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Transcription factors from multiple families ensure enhancer selectivity and robust neuron terminal differentiation Angela Jimeno-Martín, Erick Sousa, Noemi Daroqui, Rebeca Brocal-Ruiz, Miren Maicas, Nuria Flames* Developmental Neurobiology Unit, Instituto de Biomedicina de Valencia IBV- CSIC, Valencia, 46010, Spain * Correspondence: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.09.04.283036; this version posted September 4, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 SUMMARY 2 To search for general principles underlying neuronal regulatory programs we 3 built an RNA interference library against all transcription factors (TFs) encoded 4 in C. elegans genome and systematically screened for specification defects in 5 ten different neuron types of the monoaminergic (MA) superclass. 6 We identified over 90 TFs involved in MA specification, with at least ten different 7 TFs controlling differentiation of each individual neuron type. These TFs belong 8 predominantly to five TF families (HD, bHLH, ZF, bZIP and NHR). Next, 9 focusing on the complexity of terminal differentiation, we identified and 10 functionally characterized the dopaminergic terminal regulatory program. We 11 found that seven TFs from four different families act in a TF collective to provide 12 genetic robustness and to impose a specific gene regulatory signature enriched 13 in the regulatory regions of dopamine effector genes.
    [Show full text]
  • Assessment of Mtor-Dependent Translational Regulation Of
    Assessment of mTOR-Dependent Translational Regulation of Interferon Stimulated Genes Mark Livingstone, Kristina Sikström, Philippe Robert, Gilles Uzé, Ola Larsson, Sandra Pellegrini To cite this version: Mark Livingstone, Kristina Sikström, Philippe Robert, Gilles Uzé, Ola Larsson, et al.. Assessment of mTOR-Dependent Translational Regulation of Interferon Stimulated Genes. PLoS ONE, Public Library of Science, 2015, 10 (7), pp.e0133482. 10.1371/journal.pone.0133482. pasteur-02136942 HAL Id: pasteur-02136942 https://hal-pasteur.archives-ouvertes.fr/pasteur-02136942 Submitted on 22 May 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License RESEARCH ARTICLE Assessment of mTOR-Dependent Translational Regulation of Interferon Stimulated Genes Mark Livingstone1¤, Kristina Sikström2, Philippe A. Robert1, Gilles Uzé3, Ola Larsson2*, Sandra Pellegrini1* 1 Cytokine Signaling Unit, Institut Pasteur, CNRS URA1961, Paris, France, 2 Department of Oncology- Pathology, Karolinska Institutet, Stockholm, Sweden, 3 CNRS UMR5235, University of Montpellier II, Montpellier, France ¤ Current Address: tebu-bio SAS, 39 rue de Houdan—BP 15, 78612 Le Perray-en-Yvelines Cedex, France * [email protected] (SP); [email protected] (OL) Abstract Type-I interferon (IFN)-induced activation of the mammalian target of rapamycin (mTOR) OPEN ACCESS signaling pathway has been implicated in translational control of mRNAs encoding inter- Citation: Livingstone M, Sikström K, Robert PA, Uzé feron-stimulated genes (ISGs).
    [Show full text]
  • Supplementary Materials
    Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine
    [Show full text]