Non-Coding RNAs: A Dynamic and Complex Network of Gene Regulation

It has been estimated that less than two percent of the mammalian genome encodes proteins, rest of the genome which was earlier considered as junk DNA is the treasure trove of non-coding RNAs (ncRNAs). Many ncRNAs have now been characterized. They constitute one of the largest families of gene regulators that are found in plants and animals. They form a complex network and have key roles in diverse regulatory pathways involved in human health and disease. In this review, different types of ncRNAs, their biogenesis, structure, function and evolutionary significance is showcased

[1]  S. Swaminathan Noncoding RNAs produced by oncogenic human herpesviruses , 2008, Journal of cellular physiology.

[2]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[3]  C. Croce,et al.  miR-15 and miR-16 induce apoptosis by targeting BCL2. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[4]  H. Lage,et al.  Modulation of the classical multidrug resistance (MDR) phenotype by RNA interference (RNAi) , 2003, FEBS letters.

[5]  C. Kanduri,et al.  Epigenetics of imprinted long noncoding RNAs. , 2009, Epigenetics.

[6]  J. Mattick,et al.  The evolution of controlled multitasked gene networks: the role of introns and other noncoding RNAs in the development of complex organisms. , 2001, Molecular biology and evolution.

[7]  W. Filipowicz,et al.  Relief of microRNA-Mediated Translational Repression in Human Cells Subjected to Stress , 2006, Cell.

[8]  Manel Esteller,et al.  MicroRNAs and cancer epigenetics: a macrorevolution , 2010, Current opinion in oncology.

[9]  M. Leeb,et al.  Mechanistic concepts in X inactivation underlying dosage compensation in mammals , 2010, Heredity.

[10]  N. Niikawa,et al.  Neuron-specific relaxation of Igf2r imprinting is associated with neuron-specific histone modifications and lack of its antisense transcript Air. , 2005, Human molecular genetics.

[11]  J. Goodrich,et al.  From bacteria to humans, chromatin to elongation, and activation to repression: The expanding roles of noncoding RNAs in regulating transcription , 2009, Critical reviews in biochemistry and molecular biology.

[12]  J. Mattick,et al.  Long non-coding RNAs: insights into functions , 2009, Nature Reviews Genetics.

[13]  A. Butte,et al.  Open Access Research Article Predicting Environmental Chemical Factors Associated with Disease-related Gene Expression Data , 2022 .

[14]  Paulo P. Amaral,et al.  RNA regulation of epigenetic processes , 2009, BioEssays : news and reviews in molecular, cellular and developmental biology.

[15]  Michael T. McManus,et al.  Dysregulation of Cardiogenesis, Cardiac Conduction, and Cell Cycle in Mice Lacking miRNA-1-2 , 2007, Cell.

[16]  D. Chitwood,et al.  Small RNAs are on the move , 2010, Nature.

[17]  C. Sander,et al.  A novel class of small RNAs bind to MILI protein in mouse testes , 2006, Nature.

[18]  M. Fabbri,et al.  MicroRNAs and genomic variations: from Proteus tricks to Prometheus gift. , 2009, Carcinogenesis.

[19]  P. Anderson,et al.  RNA granules: post-transcriptional and epigenetic modulators of gene expression , 2009, Nature Reviews Molecular Cell Biology.

[20]  R. Grillari‐Voglauer,et al.  Novel modulators of senescence, aging, and longevity: Small non-coding RNAs enter the stage , 2010, Experimental Gerontology.

[21]  R. Allshire,et al.  Kinetochore and heterochromatin domains of the fission yeast centromere , 2004, Chromosome Research.

[22]  K. Steel,et al.  MicroRNAs in mouse development and disease , 2010, Seminars in cell & developmental biology.

[23]  Michael Q. Zhang,et al.  Regulating Gene Expression through RNA Nuclear Retention , 2005, Cell.

[24]  Yuriy Gusev,et al.  Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors. , 2007, RNA.

[25]  J. M. Thomson,et al.  Argonaute2 Is the Catalytic Engine of Mammalian RNAi , 2004, Science.

[26]  E. Heard,et al.  X inactivation and the complexities of silencing a sex chromosome. , 2009, Current opinion in cell biology.

[27]  P. Sætrom,et al.  MicroRNA-directed transcriptional gene silencing in mammalian cells , 2008, Proceedings of the National Academy of Sciences.

[28]  W. Filipowicz,et al.  Molecular biology: The expanding world of small RNAs , 2008, Nature.

[29]  M. Kyba,et al.  The H19 lincRNA is a developmental reservoir of miR-675 which suppresses growth and Igf1r , 2012, Nature Cell Biology.

[30]  F. Costa,et al.  Non-coding RNAs, epigenetics and complexity. , 2008, Gene.

[31]  Brian Luke,et al.  TERRA: telomeric repeat-containing RNA , 2009, The EMBO journal.

[32]  Ali Nahvi,et al.  A Parsimonious Model for Gene Regulation by miRNAs , 2011, Science.

[33]  P. Gounon,et al.  RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse , 2006, Nature.

[34]  A. Naqvi,et al.  The Fascinating World of RNA Interference , 2009, International journal of biological sciences.

[35]  V. Chandler Paramutation: From Maize to Mice , 2007, Cell.

[36]  Z. Herceg,et al.  Oncogenic microRNAs (OncomiRs) as a new class of cancer biomarkers , 2010, BioEssays : news and reviews in molecular, cellular and developmental biology.

[37]  Takahide Yokoi,et al.  Transcripts of unknown function in multiple-signaling pathways involved in human stem cell differentiation , 2009, Nucleic acids research.

[38]  S. Baylin,et al.  DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci , 2000, Nature Genetics.

[39]  Ž. Pezer,et al.  Role of non-coding RNA and heterochromatin in aneuploidy and cancer. , 2008, Seminars in cancer biology.

[40]  N. Bonini,et al.  MicroRNA pathways modulate polyglutamine-induced neurodegeneration. , 2006, Molecular cell.

[41]  Shuta Tomida,et al.  Reduced expression of Dicer associated with poor prognosis in lung cancer patients , 2005, Cancer science.

[42]  J. Rinn,et al.  A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response , 2010, Cell.

[43]  A. Hatzigeorgiou,et al.  Anti-apoptotic function of a microRNA encoded by the HSV-1 latency-associated transcript , 2008, Nature.

[44]  A. Aravin,et al.  PIWI-interacting small RNAs: the vanguard of genome defence , 2011, Nature Reviews Molecular Cell Biology.

[45]  C. Croce,et al.  Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[46]  G. Hannon,et al.  A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases , 2008, Nature Structural &Molecular Biology.

[47]  Laurence Ettwiller,et al.  Large-scale analysis of the regulatory architecture of the mouse genome with a transposon-associated sensor , 2011, Nature Genetics.

[48]  S. Stamm,et al.  Regulation of alternative splicing by short non-coding nuclear RNAs , 2010, RNA biology.

[49]  Daniel B. Martin,et al.  Circulating microRNAs as stable blood-based markers for cancer detection , 2008, Proceedings of the National Academy of Sciences.

[50]  G. Karpen,et al.  Epigenetic regulation of centromeric chromatin: old dogs, new tricks? , 2008, Nature Reviews Genetics.

[51]  Izumi Horikawa,et al.  Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescence. , 2008, Cancer research.

[52]  R. Stephens,et al.  Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. , 2006, Cancer cell.

[53]  W. Hennig The revolution of the biology of the genome , 2004, Cell Research.

[54]  C. Bond,et al.  Paraspeckles: nuclear bodies built on long noncoding RNA , 2009, The Journal of cell biology.

[55]  Kirandeep Kaur,et al.  Cellular Physiology Cellular Physiology Cellular Physiology Cellular Physiology Cellular Physiology Micrornas in Diabetes: Tiny Players in Big Disease , 2022 .

[56]  E. Heard,et al.  A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced. , 2006, Genes & development.

[57]  C. Sander,et al.  A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing , 2007, Cell.

[58]  Ji Wu,et al.  MicroRNAs and regenerative medicine. , 2007, DNA and cell biology.

[59]  A. Clark,et al.  Population dynamics of PIWI-interacting RNAs (piRNAs) and their targets in Drosophila. , 2010, Genome research.

[60]  T. Golub,et al.  Impaired microRNA processing enhances cellular transformation and tumorigenesis , 2007, Nature Genetics.

[61]  Jeannie T. Lee,et al.  A functional role for Tsix transcription in blocking Xist RNA accumulation but not in X-chromosome choice , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[62]  D. S. Gross,et al.  Chromatin , 2020, Definitions.

[63]  Yvonne Tay,et al.  MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation , 2008, Nature.

[64]  Michael F. Lin,et al.  Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals , 2009, Nature.

[65]  Robin D. Dowell,et al.  Toggle involving cis-interfering noncoding RNAs controls variegated gene expression in yeast , 2009, Proceedings of the National Academy of Sciences.

[66]  Taous Khan,et al.  MicroRNAs: synthesis, mechanism, function, and recent clinical trials. , 2010, Biochimica et biophysica acta.

[67]  Sun-Chong Wang,et al.  Age-Specific Epigenetic Drift in Late-Onset Alzheimer's Disease , 2008, PloS one.

[68]  Christopher M. Gallo,et al.  Processing bodies and germ granules are distinct RNA granules that interact in C. elegans embryos. , 2008, Developmental biology.

[69]  M. Fraga,et al.  Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. , 2007, Cancer research.

[70]  Anton P. McCaffrey,et al.  Advances in microRNAs: implications for gene therapists. , 2008, Human gene therapy.

[71]  Gaurav Kumar Pandey,et al.  Regulation of the mammalian epigenome by long noncoding RNAs. , 2009, Biochimica et biophysica acta.

[72]  C. Ponting,et al.  Evolution and Functions of Long Noncoding RNAs , 2009, Cell.

[73]  Miao Sun,et al.  MicroRNA and cancer: Current status and prospective , 2006, International journal of cancer.

[74]  W. Filipowicz,et al.  The widespread regulation of microRNA biogenesis, function and decay , 2010, Nature Reviews Genetics.

[75]  M. Szcześniak,et al.  lncRNA-RNA Interactions across the Human Transcriptome , 2016, PloS one.

[76]  L. Denby,et al.  Targeting non-coding RNA for the therapy of renal disease. , 2016, Current opinion in pharmacology.

[77]  S. Lowe,et al.  A microRNA polycistron as a potential human oncogene , 2005, Nature.

[78]  F. Costa,et al.  Non-coding RNAs: new players in eukaryotic biology. , 2005, Gene.

[79]  J. Lawrence,et al.  Loss of miRNA biogenesis induces p19Arf-p53 signaling and senescence in primary cells , 2008, The Journal of cell biology.

[80]  Antonin Morillon,et al.  Pervasive transcription constitutes a new level of eukaryotic genome regulation , 2009, EMBO reports.

[81]  K. Morris,et al.  Controlling transcription with noncoding RNAs in mammalian cells. , 2010, BioTechniques.

[82]  Fischer L Tan,et al.  RNAi, a new therapeutic strategy against viral infection , 2004, Cell Research.

[83]  B. Reinhart,et al.  A biochemical framework for RNA silencing in plants. , 2003, Genes & development.

[84]  J. Rinn,et al.  Large non-coding RNAs: missing links in cancer? , 2010, Human molecular genetics.

[85]  J. Mattick,et al.  Small regulatory RNAs in mammals. , 2005, Human molecular genetics.

[86]  J. Sedat,et al.  Direct Evidence of a Role for Heterochromatin in Meiotic Chromosome Segregation , 1996, Cell.

[87]  Sean J. Morrison,et al.  Hmga2 Promotes Neural Stem Cell Self-Renewal in Young but Not Old Mice by Reducing p16Ink4a and p19Arf Expression , 2008, Cell.

[88]  Anthony K. L. Leung,et al.  Quantitative analysis of Argonaute protein reveals microRNA-dependent localization to stress granules , 2006, Proceedings of the National Academy of Sciences.

[89]  M. Krangel,et al.  Noncoding transcription controls downstream promoters to regulate T‐cell receptor α recombination , 2007, The EMBO journal.

[90]  Ravi Sachidanandam,et al.  Developmentally Regulated piRNA Clusters Implicate MILI in Transposon Control , 2007, Science.

[91]  C. Burge,et al.  Prediction of Mammalian MicroRNA Targets , 2003, Cell.

[92]  J. Easton,et al.  Duplication of a genomic region containing the Cdc2L1-2 and MMP21-22 genes on human chromosome 1p36.3 and their linkage to D1Z2. , 1998, Genome research.

[93]  H. Willard,et al.  X-inactivation profile reveals extensive variability in X-linked gene expression in females , 2005, Nature.

[94]  L. Singh,et al.  Novel noncoding RNA from human Y distal heterochromatic block (Yq12) generates testis-specific chimeric CDC2L2. , 2007, Genome research.

[95]  A. Bradley,et al.  Identification of mammalian microRNA host genes and transcription units. , 2004, Genome research.

[96]  G. Karpen,et al.  H3K9 methylation and RNA interference regulate nucleolar organization and repeated DNA stability , 2007, Nature Cell Biology.

[97]  E. Gibney,et al.  Epigenetics and gene expression , 2010, Heredity.

[98]  J. Sedivy,et al.  Epigenetic control of aging. , 2011, Antioxidants & redox signaling.

[99]  Jian Gu,et al.  Genetic Variations in MicroRNA-Related Genes Are Novel Susceptibility Loci for Esophageal Cancer Risk , 2008, Cancer Prevention Research.

[100]  J. Steitz,et al.  AU-Rich-Element-Mediated Upregulation of Translation by FXR1 and Argonaute 2 , 2007, Cell.

[101]  Phillip A. Sharp,et al.  Emerging Roles for Natural MicroRNA Sponges , 2010, Current Biology.

[102]  J. Castle,et al.  Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs , 2005, Nature.

[103]  Ru Huang,et al.  The function of non-coding RNAs in genomic imprinting , 2009, Development.

[104]  Guisheng Song,et al.  MiR-433 and miR-127 Arise from Independent Overlapping Primary Transcripts Encoded by the miR-433-127 Locus , 2008, PloS one.

[105]  D. Barlow,et al.  Genomic imprinting mechanisms in embryonic and extraembryonic mouse tissues , 2010, Heredity.

[106]  X. Li,et al.  Transcriptional regulation of mammalian miRNA genes. , 2011, Genomics.

[107]  A. Bird,et al.  Densely methylated sequences that are preferentially localized at telomere-proximal regions of human chromosomes. , 1999, Gene.

[108]  Howard Y. Chang,et al.  Long noncoding RNA HOTAIR reprograms chromatin state to promote cancer metastasis , 2010, Nature.

[109]  S. Choudhuri Lesser known relatives of miRNA. , 2009, Biochemical and biophysical research communications.

[110]  Andrew R. Bassett,et al.  Extraordinary transgressive phenotypes of hybrid tomato are influenced by epigenetics and small silencing RNAs , 2012, The EMBO journal.

[111]  T. de Lange Telomere-related genome instability in cancer. , 2005, Cold Spring Harbor symposia on quantitative biology.

[112]  W. Filipowicz,et al.  Proteomics Joins the Search for MicroRNA Targets , 2008, Cell.

[113]  D. Weigel,et al.  Transcriptional Control of Gene Expression by MicroRNAs , 2010, Cell.

[114]  George A Calin,et al.  Chromosomal rearrangements and microRNAs: a new cancer link with clinical implications. , 2007, The Journal of clinical investigation.

[115]  Claes Wahlestedt,et al.  MicroRNA-219 modulates NMDA receptor-mediated neurobehavioral dysfunction , 2009, Proceedings of the National Academy of Sciences.

[116]  Stefano Piccolo,et al.  MicroRNA control of signal transduction , 2010, Nature Reviews Molecular Cell Biology.

[117]  Peter T. Nelson,et al.  MicroRNAs (miRNAs) in Neurodegenerative Diseases , 2008, Brain pathology.

[118]  John N. Hutchinson,et al.  An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. , 2009, Molecular cell.

[119]  S. Nasi,et al.  Non coding RNA and brain , 2006, BMC Neuroscience.

[120]  S. Grewal,et al.  Heterochromatin Regulates Cell Type-Specific Long-Range Chromatin Interactions Essential for Directed Recombination , 2004, Cell.

[121]  Lubo Zhang,et al.  Maternal Cocaine Administration Causes an Epigenetic Modification of Protein Kinase Cϵ Gene Expression in Fetal Rat Heart , 2007, Molecular Pharmacology.

[122]  J. Mattick,et al.  The relationship between non-protein-coding DNA and eukaryotic complexity. , 2007, BioEssays : news and reviews in molecular, cellular and developmental biology.

[123]  Jeannie T. Lee,et al.  X chromosome dosage compensation: how mammals keep the balance. , 2008, Annual review of genetics.

[124]  M. Cairns,et al.  Dysregulation of miRNA 181b in the temporal cortex in schizophrenia. , 2008, Human molecular genetics.

[125]  Jana Hertel,et al.  Non-Coding RNAs , 2008, Cellular Oncology : the Official Journal of the International Society for Cellular Oncology.

[126]  M. Esteller Non-coding RNAs in human disease , 2011, Nature Reviews Genetics.

[127]  I. Weaver,et al.  The Transcription Factor Nerve Growth Factor-Inducible Protein A Mediates Epigenetic Programming: Altering Epigenetic Marks by Immediate-Early Genes , 2007, The Journal of Neuroscience.

[128]  Leighton J. Core,et al.  Nascent RNA Sequencing Reveals Widespread Pausing and Divergent Initiation at Human Promoters , 2008, Science.

[129]  J. Cohen,et al.  An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor , 2008, Proceedings of the National Academy of Sciences.

[130]  P. Zamore,et al.  Somatic piRNA biogenesis , 2010, The EMBO journal.

[131]  F. Cuzin,et al.  Inherited variation at the epigenetic level: paramutation from the plant to the mouse. , 2008, Current opinion in genetics & development.

[132]  F. Slack,et al.  RAS Is Regulated by the let-7 MicroRNA Family , 2005, Cell.

[133]  Jeannie T. Lee,et al.  Long Noncoding RNAs: Past, Present, and Future , 2013, Genetics.

[134]  Yi Liu,et al.  qiRNA is a new type of small interfering RNA induced by DNA damage , 2009, Nature.

[135]  R. F. Luco,et al.  Epigenetics in Alternative Pre-mRNA Splicing , 2011, Cell.

[136]  C. Burge,et al.  The Widespread Impact of Mammalian MicroRNAs on mRNA Repression and Evolution , 2005, Science.

[137]  Fumiaki Sato,et al.  MicroRNAs and epigenetics , 2011, The FEBS journal.

[138]  M. Takeichi,et al.  The mRNA-like noncoding RNA Gomafu constitutes a novel nuclear domain in a subset of neurons , 2007, Journal of Cell Science.

[139]  J. Weiler,et al.  Anti-miRNA oligonucleotides (AMOs): ammunition to target miRNAs implicated in human disease? , 2006, Gene Therapy.

[140]  Manolis Kellis,et al.  Discrete Small RNA-Generating Loci as Master Regulators of Transposon Activity in Drosophila , 2007, Cell.

[141]  Gene W. Yeo,et al.  Divergent Transcription from Active Promoters , 2008, Science.

[142]  D. Tautz,et al.  The evolutionary origin of orphan genes , 2011, Nature Reviews Genetics.

[143]  G. Hannon,et al.  A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases , 2008, Nature Structural &Molecular Biology.

[144]  A. Feinberg,et al.  Loss of imprinting of IGF2: a common epigenetic modifier of intestinal tumor risk. , 2005, Cancer research.

[145]  K. Roemer,et al.  Epstein–Barr virus-encoded microRNA miR-BART2 down-regulates the viral DNA polymerase BALF5 , 2007, Nucleic acids research.

[146]  James A. Birchler,et al.  Heterochromatic Silencing and HP1 Localization in Drosophila Are Dependent on the RNAi Machinery , 2004, Science.

[147]  G. Carmichael,et al.  Altered nuclear retention of mRNAs containing inverted repeats in human embryonic stem cells: functional role of a nuclear noncoding RNA. , 2009, Molecular cell.

[148]  J. Haier,et al.  MicroRNAs: predictors and modifiers of chemo- and radiotherapy in different tumour types. , 2010, European journal of cancer.

[149]  B. Cullen,et al.  Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. , 2003, Genes & development.

[150]  Xiang-Dong Fu,et al.  Chromatin: the final frontier in splicing regulation? , 2010, Developmental cell.

[151]  R. Allshire,et al.  Requirement of Heterochromatin for Cohesion at Centromeres , 2001, Science.

[152]  T. Hassold,et al.  Nondisjunction--a view from ringside. , 2004, The New England journal of medicine.

[153]  Mariette Schrier,et al.  A Genetic Screen Implicates miRNA-372 and miRNA-373 As Oncogenes in Testicular Germ Cell Tumors , 2006, Cell.

[154]  D. Spector,et al.  Long noncoding RNAs: functional surprises from the RNA world. , 2009, Genes & development.

[155]  L. Lim,et al.  A microRNA component of the p53 tumour suppressor network , 2007, Nature.

[156]  N. Jamieson,et al.  Pathway analysis of senescence-associated miRNA targets reveals common processes to different senescence induction mechanisms. , 2009, Biochimica et biophysica acta.

[157]  C. Croce,et al.  MicroRNAs in cancer: small molecules with a huge impact. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[158]  C. Croce,et al.  MicroRNA signatures in human cancers , 2006, Nature Reviews Cancer.

[159]  Tsung-Cheng Chang,et al.  Widespread microRNA repression by Myc contributes to tumorigenesis , 2008, Nature Genetics.