Antisense Transcripts With FANTOM2 Clone Set and Their Implications for Gene Regulation

Kiyosawa, Hidenori; Yamanaka, Itaru; Osato, Naoki; Kondo, Shinji; Hayashizaki, Yoshihide

doi:10.1101/gr.982903

Cited by 235 publications

(217 citation statements)

References 117 publications

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“…They can be transcribed in cis, from opposing DNA strands at the same genomic locus, or in trans, from distinct loci. In humans, between 5 and 10% of all genes were found to have a cis antisense counterpart (28)(29)(30), and similar results were reported in mouse (31), and Drosophila (32). It is tantalizing to hypothesize that sense-antisense RNA-transcript pairs create dsRNA duplexes that undergo extensive A-to-I RNA editing.…”

Section: Adar Targets From Intermolecular Pairs Of Sense and Antisenssupporting

confidence: 67%

Origins and evolution of ADAR‐mediated RNA editing

2009

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SummaryAdenosine deaminases acting on RNA (ADARs) convert adenosines to inosines in double-stranded RNA in animals. Identification of more ADAR targets and genome sequences of diverse eukaryotes present an opportunity to elucidate the origin and evolution of ADAR-mediated RNA editing. Comparative analysis of the adenosine deaminase family indicates that the first ADAR might have evolved from adenosine deaminases acting on tRNAs after the split of protozoa and metazoa. ADAR1 and ADAR2 arose by gene duplications in early metazoan evolution, 700 million years ago, while ADAR3 and TENR might originate after Urochordata-Vertebrata divergence. More ADAR or ADAR-like genes emerged in some animals (e.g., fish). Considering the constrained structure, ADAR targets are proposed to have evolved from transposable elements and repeats, random selection, and fixation, and intermolecular pairs of sense and antisense RNA. In some degree, increased ADAR-mediated gene regulation should substantially contribute to the emergence and evolution of complex metazoans, particularly the nervous system.2009 IUBMB IUBMB Life, 61(6): 572-578, 2009

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Section: Adar Targets From Intermolecular Pairs Of Sense and Antisenssupporting

confidence: 67%

Origins and evolution of ADAR‐mediated RNA editing

2009

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“…Recent genome-wide analyses suggest that as much as 15%-25% of human genes might be involved in antisense transcription (http://www.narna.ncl.ac.uk). Similar analyses in other organisms including mouse have revealed a large number of NATs (Kiyosawa et al 2003(Kiyosawa et al , 2005Lavorgna et al 2004;Katayama et al 2005). NATs are RNAs containing sequences that are complementary to other endogenous RNAs.…”

Section: Natural Antisense Transcripts (Nats): New Players In the Genmentioning

confidence: 87%

Eukaryotic regulatory RNAs: an answer to the ‘genome complexity’ conundrum

Prasanth¹,

Spector²

2007

Genes Dev.

365

305

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A large portion of the eukaryotic genome is transcribed as noncoding RNAs (ncRNAs). While once thought of primarily as "junk," recent studies indicate that a large number of these RNAs play central roles in regulating gene expression at multiple levels. The increasing diversity of ncRNAs identified in the eukaryotic genome suggests a critical nexus between the regulatory potential of ncRNAs and the complexity of genome organization. We provide an overview of recent advances in the identification and function of eukaryotic ncRNAs and the roles played by these RNAs in chromatin organization, gene expression, and disease etiology.

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“…A total of 2,481 sense-antisense pairs (4,962 transcriptional units) in which exons from both transcriptional units overlapped were identified. In 351 of these pairs, neither transcriptional unit seems to encode a protein product, whereas in 519 pairs, both are coding 6 . Another 899 pairs (1,798 transcriptional units) in which the overlap was between an exon and an intron were identified.…”

Section: Rna-directed Dna Read-outmentioning

confidence: 99%

“…This mechanism might be quite general. A search for imprinted genes identified 159 differentially expressed loci with SATs 51 , and an examination of 58 known mouse imprinted genes found an antisense transcript for 22 of them 6 . Besides acting on themselves, SATs may cause differential expression of other loci by silencing genes in adjacent chromosomal regions.…”

Section: Rna-directed Dna Read-outmentioning

confidence: 99%

The four Rs of RNA-directed evolution

Herbert

2003

Nat Genet

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The read-out of genetic information in eukaryotes is not only more complex than previously realized, but also more dynamic. Much of the information is 'soft-wired' , with extensive RNA processing necessary to generate phenotypes 10 . A subset of the RNA, referred to here as coRNA ( Fig. 1), coordinates the read-out of genetic information and reconciles regulatory inputs. For each cell type, the sum of these interactions defines a distinct RNA profile or ribotype 10 . RNA-based processes also facilitate replication of ribotypes in subsequent generations. The flexibility of these programs allows soft-wired organisms to evolve in a more rapid and dynamic way than 'hard-wired' organisms constrained by DNA mutation 10 . Together, the actions of reading, 'riting, 'rithmetic and replication constitute the four Rs of RNA-directed evolution. Here, we describe roles for coRNAs and SATs (Fig. 2) in these events. RNA-directed RNA readoutRNA coregulates the sequence-specific read-out of genetic information from RNA by targeting the evolutionarily conserved machinery of RNA interference (RNAi) 11 and translational repression. RNAi leading to post-transcriptional gene silencing (PTGS) is induced by doublestranded RNA (dsRNA) arising from infection by dsRNA viruses, senseantisense transcription pairs, transcription of inverted repeats and delivery of dsRNAs manufactured in vitro 12 . Both endogenous and exogenous dsRNAs are processed cytoplasmically by RNase III dicer paralogs into small interfering RNAs (siRNAs) that are 21-25 bases long 12,13 . These siRNAs are incorporated into an RNA-induced silencing complex (RISC) that targets any RNA with a sequence complementary to the siRNA 12,14 . The target RNA is cleaved by RISC, which has endonucleolytic and presumed exonucleolytic activity 12,15 . Each cycle results in the destruction of the target RNA and the regeneration of an active RISC 16,17 .In Neurospora crassa 18,19 , plants 20 , Schizosaccharomyces pombe 21 and Caenorhabditis elegans 22 , but not in flies, humans or mouse oocyctes 18,19,23,24 , PTGS can also be initiated by an RNA-dependent RNA polymerase (RdRP) that synthesizes complementary RNA from highly expressed transcripts to generate dsRNA. This process can spread from the 3´ to the 5´ end of the mRNA, leading to progressive silencing of a gene and other mRNAs with exons in common (transitive RNAi) 18,22 . From the evolutionary viewpoint, transitive RNAi favors the generation of new phenotypes, as related genes in species with polyploid genomes will escape cosuppression by sequence divergence, resulting in altered function or expression.The number of dicer paralogs also differs between species. Arabidopsis, which has at least four dicer family members, seems to use different enzymes to defend against viruses and to process endogenously produced dsRNA 13,25 . In humans, mice and worms, there is only one dicer ortholog, suggesting that any pathway-specific functions are guided by ancillary regulatory proteins associated with RISC. These ancillary proteins include me...

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Antisense Transcripts With FANTOM2 Clone Set and Their Implications for Gene Regulation

Cited by 235 publications

References 117 publications

Origins and evolution of ADAR‐mediated RNA editing

Origins and evolution of ADAR‐mediated RNA editing

Eukaryotic regulatory RNAs: an answer to the ‘genome complexity’ conundrum

The four Rs of RNA-directed evolution

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