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The Complexity of the Mammalian Transcriptome

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Long Noncoding RNA

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1363))

Abstract

Draft genome assemblies for multiple mammalian species combined with new technologies to map transcripts from diverse RNA samples to these genomes developed in the early 2000s revealed that the mammalian transcriptome was vastly larger and more complex than previously anticipated. Efforts to comprehensively catalog the identity and features of transcripts present in a variety of species, tissues and cell lines revealed that a large fraction of the mammalian genome is transcribed in at least some settings. A large number of these transcripts encode long non-coding RNAs (lncRNAs). Many lncRNAs overlap or are anti-sense to protein coding genes and others overlap small RNAs. However, a large number are independent of any previously known mRNA or small RNA. While the functions of a majority of these lncRNAs are unknown, many appear to play roles in gene regulation. Many lncRNAs have species-specific and cell type specific expression patterns and their evolutionary origins are varied. While technological challenges have hindered getting a full picture of the diversity and transcript structure of all of the transcripts arising from lncRNA loci, new technologies including single molecule nanopore sequencing and single cell RNA sequencing promise to generate a comprehensive picture of the mammalian transcriptome.

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References

  1. Bartolomei MS, Zemel S, Tilghman SM (1991) Parental imprinting of the mouse H19 gene. Nature 351:153–155. https://doi.org/10.1038/351153a0

    Article  CAS  PubMed  Google Scholar 

  2. Bose DA, Donahue G, Reinberg D et al (2017) RNA binding to CBP stimulates histone acetylation and transcription. Cell 168:135–149..e22. https://doi.org/10.1016/j.cell.2016.12.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Boyd SD (2008) Everything you wanted to know about small RNA but were afraid to ask. Lab Investig 88:569–578. https://doi.org/10.1038/labinvest.2008.32

    Article  CAS  PubMed  Google Scholar 

  4. Brown CJ, Ballabio A, Rupert JL et al (1991) A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature 349:38–44. https://doi.org/10.1038/349038a0

    Article  CAS  PubMed  Google Scholar 

  5. Cabili MN, Trapnell C, Goff L et al (2011) Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev 25:1915–1927. https://doi.org/10.1101/gad.17446611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Carninci P, Kasukawa T, Katayama S et al (2005) The transcriptional landscape of the mammalian genome. Science 309:1559–1563. https://doi.org/10.1126/science.1112014

    Article  CAS  PubMed  Google Scholar 

  7. Cawley S, Bekiranov S, Ng HH et al (2004) Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 116:499–509. https://doi.org/10.1016/s0092-8674(04)00127-8

    Article  CAS  PubMed  Google Scholar 

  8. Cheng J, Kapranov P, Drenkow J et al (2005) Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science 308:1149–1154. https://doi.org/10.1126/science.1108625

    Article  CAS  PubMed  Google Scholar 

  9. Cole C, Byrne A, Adams M et al (2020) Complete characterization of the human immune cell transcriptome using accurate full-length cDNA sequencing. Genome Res 30:589–601. https://doi.org/10.1101/gr.257188.119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Darmanis S, Sloan SA, Zhang Y et al (2015) A survey of human brain transcriptome diversity at the single cell level. Proc Natl Acad Sci U S A 112:7285–7290. https://doi.org/10.1073/pnas.1507125112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Derrien T, Johnson R, Bussotti G et al (2012) The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22:1775–1789. https://doi.org/10.1101/gr.132159.111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Djebali S, Davis CA, Merkel A et al (2012) Landscape of transcription in human cells. Nature 489:101–108. https://doi.org/10.1038/nature11233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Dougherty ML, Nuttle X, Penn O et al (2017) The birth of a human-specific neural gene by incomplete duplication and gene fusion. Genome Biol 18:49. https://doi.org/10.1186/s13059-017-1163-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Durruthy-Durruthy R, Ray M (2018) Using Fluidigm C1 to generate single-cell full-length cDNA libraries for mRNA sequencing. Methods Mol Biol 1706:199–221. https://doi.org/10.1007/978-1-4939-7471-9_11

    Article  CAS  PubMed  Google Scholar 

  15. Eiraku M, Watanabe K, Matsuo-Takasaki M et al (2008) Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. Cell Stem Cell 3:519–532. https://doi.org/10.1016/j.stem.2008.09.002

    Article  CAS  PubMed  Google Scholar 

  16. Elisaphenko EA, Kolesnikov NN, Shevchenko AI et al (2008) A dual origin of the Xist gene from a protein-coding gene and a set of transposable elements. PLoS One 3:e2521. https://doi.org/10.1371/journal.pone.0002521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74. https://doi.org/10.1038/nature11247

    Article  CAS  Google Scholar 

  18. ENCODE Project Consortium, Birney E, Stamatoyannopoulos JA et al (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799–816. https://doi.org/10.1038/nature05874

    Article  CAS  Google Scholar 

  19. Eze UC, Bhaduri A, Haeussler M et al (2021) Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia. Nat Neurosci. https://doi.org/10.1038/s41593-020-00794-1

  20. Fiddes IT, Armstrong J, Diekhans M et al (2018a) Comparative Annotation Toolkit (CAT)-simultaneous clade and personal genome annotation. Genome Res 28:1029–1038. https://doi.org/10.1101/gr.233460.117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Fiddes IT, Lodewijk GA, Mooring M et al (2018b) Human-specific NOTCH2NL genes affect Notch signaling and cortical neurogenesis. Cell 173:1356–1369.e22. https://doi.org/10.1016/j.cell.2018.03.051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Field A, Adelman K (2020) Evaluating enhancer function and transcription. Annu Rev Biochem. https://doi.org/10.1146/annurev-biochem-011420-095916

  23. Field AR, Jacobs FMJ, Fiddes IT et al (2019) Structurally conserved primate LncRNAs are transiently expressed during human cortical differentiation and influence cell-type-specific genes. Stem Cell Rep 12:245–257. https://doi.org/10.1016/j.stemcr.2018.12.006

    Article  CAS  Google Scholar 

  24. Frankish A, Diekhans M, Ferreira A-M et al (2019) GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res 47:D766–D773. https://doi.org/10.1093/nar/gky955

    Article  CAS  PubMed  Google Scholar 

  25. Furlan G, Rougeulle C (2016) Function and evolution of the long noncoding RNA circuitry orchestrating X-chromosome inactivation in mammals. Wiley Interdiscip Rev RNA 7:702–722. https://doi.org/10.1002/wrna.1359

    Article  CAS  PubMed  Google Scholar 

  26. Gabory A, Ripoche M-A, Yoshimizu T, Dandolo L (2006) The H19 gene: regulation and function of a non-coding RNA. Cytogenet Genome Res 113:188–193. https://doi.org/10.1159/000090831

    Article  CAS  PubMed  Google Scholar 

  27. Garalde DR, Snell EA, Jachimowicz D et al (2018) Highly parallel direct RNA sequencing on an array of nanopores. Nat Methods 15:201–206. https://doi.org/10.1038/nmeth.4577

    Article  CAS  PubMed  Google Scholar 

  28. Gibbs RA, Weinstock GM, Metzker ML et al (2004) Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428:493–521. https://doi.org/10.1038/nature02426

    Article  CAS  PubMed  Google Scholar 

  29. Gong C, Maquat LE (2011) lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3’ UTRs via Alu elements. Nature 470:284–288. https://doi.org/10.1038/nature09701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gordon D, Huddleston J, Chaisson MJP et al (2016) Long-read sequence assembly of the gorilla genome. Science 352:aae0344. https://doi.org/10.1126/science.aae0344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Harrow J, Frankish A, Gonzalez JM et al (2012) GENCODE: the reference human genome annotation for the ENCODE project. Genome Res 22:1760–1774. https://doi.org/10.1101/gr.135350.111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Heller MJ (2002) DNA microarray technology: devices, systems, and applications. Annu Rev Biomed Eng 4:129–153. https://doi.org/10.1146/annurev.bioeng.4.020702.153438

    Article  CAS  PubMed  Google Scholar 

  33. Hölzer M, Marz M (2019) De novo transcriptome assembly: a comprehensive cross-species comparison of short-read RNA-Seq assemblers. Gigascience 8. https://doi.org/10.1093/gigascience/giz039

  34. Hon C-C, Ramilowski JA, Harshbarger J et al (2017) An atlas of human long non-coding RNAs with accurate 5′ ends. Nature 543:199–204. https://doi.org/10.1038/nature21374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kapranov P, Cawley SE, Drenkow J et al (2002) Large-scale transcriptional activity in chromosomes 21 and 22. Science 296:916–919. https://doi.org/10.1126/science.1068597

    Article  CAS  PubMed  Google Scholar 

  36. Kapusta A, Kronenberg Z, Lynch VJ et al (2013) Transposable elements are major contributors to the origin, diversification, and regulation of vertebrate long noncoding RNAs. PLoS Genet 9:e1003470. https://doi.org/10.1371/journal.pgen.1003470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kelley D, Rinn J (2012) Transposable elements reveal a stem cell-specific class of long noncoding RNAs. Genome Biol 13:R107. https://doi.org/10.1186/gb-2012-13-11-r107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kim J, Abdelmohsen K, Yang X et al (2016) LncRNA OIP5-AS1/cyrano sponges RNA-binding protein HuR. Nucleic Acids Res 44:2378–2392. https://doi.org/10.1093/nar/gkw017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kleaveland B, Shi CY, Stefano J, Bartel DP (2018) A network of noncoding regulatory RNAs acts in the mammalian brain. Cell 174:350–362.e17. https://doi.org/10.1016/j.cell.2018.05.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kronenberg ZN, Fiddes IT, Gordon D et al (2018) High-resolution comparative analysis of great ape genomes. Science 360. https://doi.org/10.1126/science.aar6343

  41. Lancaster MA, Knoblich JA (2014) Generation of cerebral organoids from human pluripotent stem cells. Nat Protoc 9:2329–2340. https://doi.org/10.1038/nprot.2014.158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Lander ES, Linton LM, Birren B et al (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921. https://doi.org/10.1038/35057062

    Article  CAS  PubMed  Google Scholar 

  43. Lewis BP, Green RE, Brenner SE (2003) Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans. Proc Natl Acad Sci U S A 100:189–192. https://doi.org/10.1073/pnas.0136770100

    Article  CAS  PubMed  Google Scholar 

  44. Liu SJ, Nowakowski TJ, Pollen AA et al (2016) Single-cell analysis of long non-coding RNAs in the developing human neocortex. Genome Biol 17:67. https://doi.org/10.1186/s13059-016-0932-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Li W, Notani D, Ma Q et al (2013) Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature 498:516–520. https://doi.org/10.1038/nature12210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Loewer S, Cabili MN, Guttman M et al (2010) Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat Genet 42:1113–1117. https://doi.org/10.1038/ng.710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Maitra M, Nagy C, Turecki G (2019) Sequencing the human brain at single-cell resolution. Curr Behav Neurosci Rep 6:197–208. https://doi.org/10.1007/s40473-019-00192-3

    Article  Google Scholar 

  48. Martone R, Euskirchen G, Bertone P et al (2003) Distribution of NF-kappaB-binding sites across human chromosome 22. Proc Natl Acad Sci U S A 100:12247–12252. https://doi.org/10.1073/pnas.2135255100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Miga KH, Koren S, Rhie A et al (2020) Telomere-to-telomere assembly of a complete human X chromosome. Nature 585:79–84. https://doi.org/10.1038/s41586-020-2547-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mousavi K, Zare H, Dell’orso S et al (2013) eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci. Mol Cell 51:606–617. https://doi.org/10.1016/j.molcel.2013.07.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Mouse Genome Sequencing Consortium, Waterston RH, Lindblad-Toh K et al (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420:520–562. https://doi.org/10.1038/nature01262

    Article  CAS  Google Scholar 

  52. Ng S-Y, Johnson R, Stanton LW (2012) Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors. EMBO J 31:522–533. https://doi.org/10.1038/emboj.2011.459

    Article  CAS  PubMed  Google Scholar 

  53. Nowakowski TJ, Bhaduri A, Pollen AA et al (2017) Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex. Science 358:1318–1323. https://doi.org/10.1126/science.aap8809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Nuttle X, Giannuzzi G, Duyzend MH et al (2016) Emergence of a Homo sapiens-specific gene family and chromosome 16p11.2 CNV susceptibility. Nature 536:205–209. https://doi.org/10.1038/nature19075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ohnuki M, Tanabe K, Sutou K et al (2014) Dynamic regulation of human endogenous retroviruses mediates factor-induced reprogramming and differentiation potential. Proc Natl Acad Sci U S A 111:12426–12431. https://doi.org/10.1073/pnas.1413299111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Oikonomopoulos S, Wang YC, Djambazian H et al (2016) Benchmarking of the Oxford Nanopore MinION sequencing for quantitative and qualitative assessment of cDNA populations. Sci Rep 6:31602. https://doi.org/10.1038/srep31602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Okazaki Y, Furuno M, Kasukawa T et al (2002) Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature 420:563–573. https://doi.org/10.1038/nature01266

    Article  PubMed  Google Scholar 

  58. Pachnis V, Belayew A, Tilghman SM (1984) Locus unlinked to alpha-fetoprotein under the control of the murine raf and Rif genes. Proc Natl Acad Sci U S A 81:5523–5527. https://doi.org/10.1073/pnas.81.17.5523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Pauli A, Valen E, Lin MF et al (2012) Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis. Genome Res 22:577–591. https://doi.org/10.1101/gr.133009.111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Pollen AA, Bhaduri A, Andrews MG et al (2019) Establishing cerebral organoids as models of human-specific brain evolution. Cell 176:743–756.e17. https://doi.org/10.1016/j.cell.2019.01.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641. https://doi.org/10.1016/j.cell.2009.02.006

    Article  CAS  PubMed  Google Scholar 

  62. Rahat B, Ali T, Sapehia D, Mahajan A, Kaur J. Circulating Cell-Free Nucleic Acids as Epigenetic Biomarkers in Precision Medicine. Front Genet. 2020 Aug 11;11:844. https://doi.org/10.3389/fgene.2020.00844. PMID: 32849827; PMCID: PMC7431953

  63. Rahnamoun H, Lee J, Sun Z et al (2018) RNAs interact with BRD4 to promote enhanced chromatin engagement and transcription activation. Nat Struct Mol Biol 25:687–697. https://doi.org/10.1038/s41594-018-0102-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ramilowski JA, Yip CW, Agrawal S et al (2020) Functional annotation of human long noncoding RNAs via molecular phenotyping. Genome Res 30:1060–1072. https://doi.org/10.1101/gr.254219.119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Raveh E, Matouk IJ, Gilon M, Hochberg A (2015) The H19 long non-coding RNA in cancer initiation, progression and metastasis - a proposed unifying theory. Mol Cancer 14:184. https://doi.org/10.1186/s12943-015-0458-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Rinn JL, Euskirchen G, Bertone P et al (2003) The transcriptional activity of human Chromosome 22. Genes Dev 17:529–540. https://doi.org/10.1101/gad.1055203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Samonte RV, Eichler EE (2002) Segmental duplications and the evolution of the primate genome. Nat Rev Genet 3:65–72. https://doi.org/10.1038/nrg705

    Article  CAS  PubMed  Google Scholar 

  68. Sartorelli V, Lauberth SM (2020) Enhancer RNAs are an important regulatory layer of the epigenome. Nat Struct Mol Biol 27:521–528. https://doi.org/10.1038/s41594-020-0446-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Schena M, Shalon D, Davis RW, Brown PO (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270:467–470. https://doi.org/10.1126/science.270.5235.467

    Article  CAS  PubMed  Google Scholar 

  70. Sharon D, Tilgner H, Grubert F, Snyder M (2013) A single-molecule long-read survey of the human transcriptome. Nat Biotechnol 31:1009–1014. https://doi.org/10.1038/nbt.2705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Sigova AA, Abraham BJ, Ji X et al (2015) Transcription factor trapping by RNA in gene regulatory elements. Science 350:978–981. https://doi.org/10.1126/science.aad3346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Smith AM, Jain M, Mulroney L et al (2019) Reading canonical and modified nucleobases in 16S ribosomal RNA using nanopore native RNA sequencing. PLoS One 14:e0216709. https://doi.org/10.1371/journal.pone.0216709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Smith KN, Starmer J, Miller SC et al (2017) Long noncoding RNA moderates MicroRNA activity to maintain self-renewal in embryonic stem cells. Stem Cell Rep 9:108–121. https://doi.org/10.1016/j.stemcr.2017.05.005

    Article  CAS  Google Scholar 

  74. Soneson C, Yao Y, Bratus-Neuenschwander A et al (2019) A comprehensive examination of Nanopore native RNA sequencing for characterization of complex transcriptomes. Nat Commun 10:3359. https://doi.org/10.1038/s41467-019-11272-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Stolc V, Gauhar Z, Mason C et al (2004) A gene expression map for the euchromatic genome of Drosophila melanogaster. Science 306:655–660. https://doi.org/10.1126/science.1101312

    Article  CAS  PubMed  Google Scholar 

  76. Stolc V, Samanta MP, Tongprasit W et al (2005) Identification of transcribed sequences in Arabidopsis thaliana by using high-resolution genome tiling arrays. Proc Natl Acad Sci U S A 102:4453–4458. https://doi.org/10.1073/pnas.0408203102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Tang F, Barbacioru C, Wang Y et al (2009) mRNA-Seq whole-transcriptome analysis of a single cell. Nat Methods 6:377–382. https://doi.org/10.1038/nmeth.1315

    Article  CAS  PubMed  Google Scholar 

  78. Trapnell C, Roberts A, Goff L et al (2012) Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc 7:562–578. https://doi.org/10.1038/nprot.2012.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Tseng E, Underwood JG, Tseng E (2013) Full length cDNA sequencing on the PacBio® RS. J Biomol Tech 24:S45

    PubMed Central  Google Scholar 

  80. Ulitsky I, Shkumatava A, Jan CH et al (2011) Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell 147:1537–1550. https://doi.org/10.1016/j.cell.2011.11.055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Vlassov AV, Magdaleno S, Setterquist R, Conrad R (2012) Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 1820:940–948. https://doi.org/10.1016/j.bbagen.2012.03.017

    Article  CAS  PubMed  Google Scholar 

  82. Volden R, Palmer T, Byrne A et al (2018) Improving nanopore read accuracy with the R2C2 method enables the sequencing of highly multiplexed full-length single-cell cDNA. Proc Natl Acad Sci U S A 115:9726–9731. https://doi.org/10.1073/pnas.1806447115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Warren WC, Harris RA, Haukness M et al (2020) Sequence diversity analyses of an improved rhesus macaque genome enhance its biomedical utility. Science 370. https://doi.org/10.1126/science.abc6617

  84. Willingham AT, Gingeras TR (2006) TUF love for “junk” DNA. Cell 125:1215–1220. https://doi.org/10.1016/j.cell.2006.06.009

    Article  CAS  PubMed  Google Scholar 

  85. Workman RE, Tang AD, Tang PS et al (2019) Nanopore native RNA sequencing of a human poly(A) transcriptome. Nat Methods 16:1297–1305. https://doi.org/10.1038/s41592-019-0617-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Yamada K, Lim J, Dale JM et al (2003) Empirical analysis of transcriptional activity in the Arabidopsis genome. Science 302:842–846. https://doi.org/10.1126/science.1088305

    Article  CAS  PubMed  Google Scholar 

  87. Yelin R, Dahary D, Sorek R et al (2003) Widespread occurrence of antisense transcription in the human genome. Nat Biotechnol 21:379–386. https://doi.org/10.1038/nbt808

    Article  CAS  PubMed  Google Scholar 

  88. Yip KY, Cheng C, Bhardwaj N et al (2012) Classification of human genomic regions based on experimentally determined binding sites of more than 100 transcription-related factors. Genome Biol 13:R48. https://doi.org/10.1186/gb-2012-13-9-r48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Yu S, Cao H, Shen B, Feng J (2015) Tumor-derived exosomes in cancer progression and treatment failure. Oncotarget 6:37151–37168. https://doi.org/10.18632/oncotarget.6022

    Article  PubMed  PubMed Central  Google Scholar 

  90. Zheng GXY, Terry JM, Belgrader P et al (2017) Massively parallel digital transcriptional profiling of single cells. Nat Commun 8:14049. https://doi.org/10.1038/ncomms14049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The author wishes to thank Andrew Field for helpful discussions to define the scope of this article, and Mark Diekhans for discussions about GENCODE and for assistance generating Fig. 2.1. This work was supported by R01HG010329 and R01MH120295 to SRS.

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Correspondence to Sofie R. Salama .

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Salama, S.R. (2022). The Complexity of the Mammalian Transcriptome. In: Carpenter, S. (eds) Long Noncoding RNA. Advances in Experimental Medicine and Biology, vol 1363. Springer, Cham. https://doi.org/10.1007/978-3-030-92034-0_2

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