TERRA: telomeric repeat-containing RNA

Telomeres, the physical ends of eukaryotic chromosomes, consist of tandem arrays of short DNA repeats and a large set of specialized proteins. A recent analysis has identified telomeric repeat‐containing RNA (TERRA), a large non‐coding RNA in animals and fungi, which forms an integral component of telomeric heterochromatin. TERRA transcription occurs at most or all chromosome ends and it is regulated by RNA surveillance factors and in response to changes in telomere length. TERRA functions that are emerging suggest important roles in the regulation of telomerase and in orchestrating chromatin remodelling throughout development and cellular differentiation. The accumulation of TERRA at telomeres can also interfere with telomere replication, leading to a sudden loss of telomere tracts. Such a phenotype can be observed upon impairment of the RNA surveillance machinery or in cells from ICF (Immunodeficiency, Centromeric region instability, Facial anomalies) patients, in which TERRA is upregulated because of DNA methylation defects in the subtelomeric region. Thus, TERRA may mediate several crucial functions at the telomeres, a region of the genome that had been considered to be transcriptionally silent.

[1]  G. Rudenko,et al.  Transcription of telomere repeats in protozoa. , 1989, The EMBO journal.

[2]  J. Szostak,et al.  A mutant with a defect in telomere elongation leads to senescence in yeast , 1989, Cell.

[3]  C. Harley,et al.  Telomeres shorten during ageing of human fibroblasts , 1990, Nature.

[4]  C B Harley,et al.  Telomere length predicts replicative capacity of human fibroblasts. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[5]  H. Cooke,et al.  hnRNP A2/B1 binds specifically to single stranded vertebrate telomeric repeat TTAGGGn. , 1992, Nucleic acids research.

[6]  C B Harley,et al.  Telomere end-replication problem and cell aging. , 1992, Journal of molecular biology.

[7]  C. Burd,et al.  RNA binding specificity of hnRNP A1: significance of hnRNP A1 high‐affinity binding sites in pre‐mRNA splicing. , 1994, The EMBO journal.

[8]  D. Gottschling,et al.  Transcription of a yeast telomere alleviates telomere position effect without affecting chromosome stability. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[9]  L. Giudice,et al.  Developmental regulation of telomerase activity in human fetal tissues during gestation. , 1997, Molecular human reproduction.

[10]  C. Harley,et al.  Extension of life-span by introduction of telomerase into normal human cells. , 1998, Science.

[11]  S. Dupuis,et al.  Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase , 1998, Nature Genetics.

[12]  V. Lundblad,et al.  Cdc13 Delivers Separate Complexes to the Telomere for End Protection and Replication , 2001, Cell.

[13]  L. Carastro,et al.  Identification of delta helicase as the bovine homolog of HUPF1: demonstration of an interaction with the third subunit of DNA polymerase delta. , 2002, Nucleic acids research.

[14]  J. Lew-Smith,et al.  mRNAs Encoding Telomerase Components and Regulators Are Controlled by UPF Genes in Saccharomyces cerevisiae , 2003, Eukaryotic Cell.

[15]  P. Bucher,et al.  A Human Homolog of Yeast Est1 Associates with Telomerase and Uncaps Chromosome Ends When Overexpressed , 2003, Current Biology.

[16]  B. Snow,et al.  Functional Conservation of the Telomerase Protein Est1p in Humans , 2003, Current Biology.

[17]  J. Lew-Smith,et al.  Telomere Cap Components Influence the Rate of Senescence in Telomerase-Deficient Yeast Cells , 2004, Molecular and Cellular Biology.

[18]  T. Cech Beginning to Understand the End of the Chromosome , 2004, Cell.

[19]  G. Morcillo,et al.  Telomeric DNA sequences differentially activated by heat shock in two Chironomus subspecies , 2004, Chromosoma.

[20]  I. Solovei,et al.  The arrangement and transcription of telomere DNA sequences at the ends of lampbrush chromosomes of birds , 1994, Chromosome Research.

[21]  F. Ishikawa,et al.  Telomere Binding Protein Taz1 Establishes Swi6 Heterochromatin Independently of RNAi at Telomeres , 2005, Current Biology.

[22]  C. Azzalin,et al.  The Human RNA Surveillance Factor UPF1 Is Required for S Phase Progression and Genome Stability , 2006, Current Biology.

[23]  A. Krainer,et al.  hnRNP A1 associates with telomere ends and stimulates telomerase activity. , 2006, RNA.

[24]  E. Blackburn,et al.  Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging , 2006, Nature Medicine.

[25]  P. Avner,et al.  Nuclear mRNA Degradation Pathway(s) Are Implicated in Xist Regulation and X Chromosome Inactivation , 2006, PLoS genetics.

[26]  C. Azzalin,et al.  Telomeric Repeat–Containing RNA and RNA Surveillance Factors at Mammalian Chromosome Ends , 2007, Science.

[27]  M. Blasco The epigenetic regulation of mammalian telomeres , 2007, Nature Reviews Genetics.

[28]  J. Lingner,et al.  Protein–RNA and protein–protein interactions mediate association of human EST1A/SMG6 with telomerase , 2007, Nucleic acids research.

[29]  D. Tollervey,et al.  Trf4 targets ncRNAs from telomeric and rDNA spacer regions and functions in rDNA copy number control , 2007, The EMBO journal.

[30]  Howard Y. Chang,et al.  Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs , 2007, Cell.

[31]  Y. Segev,et al.  Hypomethylation of subtelomeric regions in ICF syndrome is associated with abnormally short telomeres and enhanced transcription from telomeric regions. , 2008, Human molecular genetics.

[32]  Wilhelm Palm,et al.  How shelterin protects mammalian telomeres. , 2008, Annual review of genetics.

[33]  J. Murnane,et al.  Telomeres Acquire Distinct Heterochromatin Characteristics during siRNA-Induced RNA Interference in Mouse Cells , 2008, Current Biology.

[34]  V. Zakian,et al.  Two Pathways Recruit Telomerase to Saccharomyces cerevisiae Telomeres , 2008, PLoS genetics.

[35]  M. Blasco,et al.  Role of TRF2 in the assembly of telomeric chromatin , 2008, Cell cycle.

[36]  M. Blasco,et al.  Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II , 2008, Nature Cell Biology.

[37]  Zhijian Li,et al.  The Rat1p 5' to 3' exonuclease degrades telomeric repeat-containing RNA and promotes telomere elongation in Saccharomyces cerevisiae. , 2008, Molecules and Cells.

[38]  C. Azzalin,et al.  Telomeres: The silence is broken , 2008, Cell cycle.

[39]  E. Gilson,et al.  Telomeric position effect: from the yeast paradigm to human pathologies? , 2008, Biochimie.

[40]  R. Chawla,et al.  The telomeric transcriptome and SMG proteins at the crossroads , 2009, Cytogenetic and Genome Research.

[41]  R. Martienssen,et al.  RNAi, heterochromatin and the cell cycle. , 2008, Trends in genetics : TIG.

[42]  Jeannie T. Lee,et al.  Polycomb Proteins Targeted by a Short Repeat RNA to the Mouse X Chromosome , 2008, Science.

[43]  M. Komiyama,et al.  Human telomere RNA and DNA form an intermolecular G-quadruplex. , 2008, Nucleic acids symposium series.

[44]  Howard Y. Chang,et al.  SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin , 2008, Nature.

[45]  E. Izaurralde,et al.  SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan. , 2008, RNA.

[46]  Jeannie T. Lee,et al.  Telomeric RNAs Mark Sex Chromosomes in Stem Cells , 2009, Genetics.

[47]  M. Malumbres,et al.  TRF1 Controls Telomere Length and Mitotic Fidelity in Epithelial Homeostasis , 2009, Molecular and Cellular Biology.

[48]  M. Blasco,et al.  Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. , 2009, Cell stem cell.

[49]  H. Pickett,et al.  Telomerase activity is associated with an increase in DNA methylation at the proximal subtelomere and a reduction in telomeric transcription , 2009, Nucleic acids research.

[50]  Robert E. Kingston,et al.  Purification of Proteins Associated with Specific Genomic Loci , 2009, Cell.

[51]  T. Jensen,et al.  SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells , 2009, Nature Structural &Molecular Biology.