Transcribed dark matter: meaning or myth?
Genomic tiling arrays, cDNA sequencing and, more recently, RNA-Seq have provided initial insights into the extent and depth of transcribed sequence across human and other genomes. These methods have led to greatly improved annotations of protein-coding genes, but have also identified transcription outside of annotated exons. One resultant issue that has aroused dispute is the balance of transcription of known exons against transcription outside of known exons. While non-genic 'dark matter' transcription was found by tiling arrays to be pervasive, it was seen to contribute only a small percentage of the polyadenylated transcriptome in some RNA-Seq experiments. This apparent contradiction has been compounded by a lack of clarity about what exactly constitutes a protein-coding gene. It remains unclear, for example, whether or not all transcripts that overlap on either strand within a genomic locus should be assigned to a single gene locus, including those that fail to share promoters, exons and splice junctions. The inability of tiling arrays and RNA-Seq to count transcripts, rather than exons or exon pairs, adds to these difficulties. While there is agreement that thousands of apparently non-coding loci are present outside of protein-coding genes in the human genome, there is vigorous debate of what constitutes evidence for their functionality. These issues will only be resolved upon the demonstration, or otherwise, that organismal or cellular phenotypes frequently result when non-coding RNA loci are disrupted.
Ponting
Chris P
CP
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK. chris.ponting@dpag.ox.ac.uk
Belgard
T Grant
TG
D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D020869:Gene Expression Profiling; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D012313:RNA / Q000235:genetics
D018076:DNA, Complementary; D012313:RNA
Nat Rev Genet. 2008 Sep;9(9):689-98
18663365
Nat Rev Genet. 2007 Jun;8(6):413-23
17486121
Nucleic Acids Res. 2010 Jan;38(Database issue):D586-92
19864252
Genome Res. 2007 Jun;17(6):682-90
17567989
Endocrinology. 2010 Jun;151(6):2443-52
20392836
Nucleic Acids Res. 2010 Jan;38(Database issue):D613-9
19906737
Genome Res. 2006 Jan;16(1):11-9
16344565
Behav Brain Res. 2004 Sep 23;154(1):273-89
15302134
Science. 2009 Jan 2;323(5910):133-8
19023044
Science. 2008 Dec 19;322(5909):1855-7
19056939
Dev Dyn. 1998 Jun;212(2):214-28
9626496
Genes Dev. 2009 Aug 15;23(16):1831-42
19684108
Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11667-72
19571010
Science. 2003 Oct 31;302(5646):842-6
14593172
PLoS Biol. 2010 May 18;8(5):e1000371
20502517
PLoS Genet. 2006 Apr;2(4):e52
16683031
Nat Biotechnol. 2010 May;28(5):511-5
20436464
Nature. 2007 Jun 14;447(7146):799-816
17571346
Nature. 2002 Dec 5;420(6915):563-73
12466851
Genome Res. 2010 Jul;20(7):899-907
20404130
Science. 2007 Jun 8;316(5830):1484-8
17510325
Nat Rev Genet. 2009 Mar;10(3):155-9
19188922
Genome Res. 2007 May;17(5):556-65
17387145
RNA. 2010 Aug;16(8):1478-87
20587619
Nature. 2004 Oct 14;431(7010):1 p following 757; discussion following 757
15495343
Science. 2005 Sep 2;309(5740):1559-63
16141072
Trends Genet. 2005 Feb;21(2):93-102
15661355
Genome Biol. 2009;10(11):R124
19895688
Nat Cell Biol. 2008 Sep;10(9):1106-13
19160492
Bioessays. 2007 Nov;29(11):1077-80
17935150
Cell. 2007 Jul 13;130(1):77-88
17632057
Trends Biochem Sci. 2005 Nov;30(11):593-9
16126390
Nat Rev Genet. 2009 Jan;10(1):57-63
19015660
Nat Nanotechnol. 2009 Apr;4(4):265-70
19350039
Nat Biotechnol. 2010 May;28(5):503-10
20436462
Genome Biol. 2010;11(5):206
20441615
Nat Struct Mol Biol. 2007 Feb;14(2):103-5
17277804
PLoS Biol. 2010 May 18;8(5):e1000370
20502697
Science. 2010 Aug 6;329(5992):689-93
20616235
Cell. 2009 Feb 20;136(4):629-41
19239885
Mol Cell. 2010 Jun 11;38(5):675-88
20542000
Cell. 2004 Feb 20;116(4):499-509
14980218
Nucleic Acids Res. 2010 Jun;38(10):e113
20150415
Nature. 2010 May 13;465(7295):182-7
20393465
Science. 2005 May 20;308(5725):1149-54
15790807
Nature. 2009 Mar 12;458(7235):223-7
19182780
PLoS Comput Biol. 2008 Nov;4(11):e1000176
19043537
Genes Dev. 2006 Jun 1;20(11):1470-84
16705037
Nat Neurosci. 2009 Aug;12(8):1020-7
19620975
Genes Dev. 2009 Jul 1;23(13):1494-504
19571179
Curr Biol. 2009 Sep 29;19(18):1527-31
19733073
PLoS Genet. 2009 Aug;5(8):e1000617
19696892
Nat Genet. 2008 Nov;40(11):1285-7
18836446
BMC Genomics. 2010 Jun 17;11:383
20565764
Brief Funct Genomic Proteomic. 2009 Nov;8(6):424-36
19833698
Genome Res. 2007 Jun;17(6):669-81
17567988