Analysis of a piwi-Related Gene Implicates Small RNAs in Genome Rearrangement in Tetrahymena

Mochizuki, Kazufumi; Fine, Noah; Fujisawa, Toshitaka; Gorovsky, Martin A.

doi:10.1016/s0092-8674(02)00909-1

Cited by 540 publications

(793 citation statements)

References 38 publications

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“…In addition, a hallmark of heterochromatin, H3K9 methylation, is spatially and temporally limited to the eliminated DNA sequences. Remarkably, targeting of regions for elimination correlates with the presence of small ,28-nt RNAs that are homologous to the regions that are lost [50,51].…”

Section: Dsrna and Heterochromatinmentioning

confidence: 99%

RNAi: an ever-growing puzzle

Denli

Hannon

2003

Trends in Biochemical Sciences

269

167

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Section: Dsrna and Heterochromatinmentioning

confidence: 99%

RNAi: an ever-growing puzzle

Denli

Hannon

2003

Trends in Biochemical Sciences

269

167

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“…Other roles for RNA-directed rewriting of DNA have been discovered in tetrahymena. This organism has two nuclei: a germline micronucleus that is transmitted to progeny and a somatic macronucleus that is actively transcribed [76][77][78] . The macronucleus is created from the micronucleus.…”

Section: Rna-directed Rewriting Of Dnamentioning

confidence: 99%

“…The macronucleus is created from the micronucleus. During this process, the deletion of DNA sequences is guided by homologous RNA transcripts from the micronucleus [76][77][78] . New sequences appearing in the macronucleus during one reproductive cycle are targeted for deletion in the next generation, ensuring, for example, that the genome is not destabilized by the spread of DNA transposons 78 .…”

Section: Rna-directed Rewriting Of Dnamentioning

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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“…Instead, these organisms use an elaborate cleavage and trans-splicing mechanism based on the action of ∼ 40nt "spliced leader" RNA. Tetrahymena appears to use an RNA-based mechanism for directing its genome-wide DNA rearrangements [286,444].…”

Section: Introductionmentioning

confidence: 99%

Evolutionary patterns of non-coding RNAs

Bompfünewerer

Flamm

Fried

et al. 2005

Theory in Biosciences

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A plethora of new functions of non-coding RNAs have been discovered in past few years. In fact, RNA is emerging as the central player in cellular regulation, taking on active roles in multiple regulatory layers from transcription, RNA maturation, and Manuscript January 2005RNA modification to translational regulation. Nevertheless, very little is known about the evolution of this "Modern RNA World" and its components. In this contribution we attempt to provide at least a cursory overview of the diversity of non-coding RNAs and functional RNA motifs in non-translated regions of regular messenger RNAs (mRNAs) with an emphasis on evolutionary questions. This survey is complemented by an in-depth analysis of examples from different classes of RNAs focusing mostly on their evolution in the vertebrate lineage. We present a survey of Y RNA genes in vertebrates, studies of the molecular evolution of the U7 snRNA, the snoRNAs E1/U17, E2, and E3, the Y RNA family, the let-7 microRNA family, and the mRNA-like evf-1 gene. We furthermore discuss the statistical distribution of microRNAs in metazoans, which suggests an explosive increase in the microRNA repertoire in vertebrates. The analysis of the transcription of non-coding RNAs (ncRNAs) suggests that small RNAs in general are genetically mobile in the sense that their association with a hostgene (e.g. when transcribed from introns of a mRNA) can change on evolutionary time scales. The let-7 family demonstrates, that even the mode of transcription (as intron or as exon) can change among paralogous ncRNA.

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Analysis of a piwi-Related Gene Implicates Small RNAs in Genome Rearrangement in Tetrahymena

Cited by 540 publications

References 38 publications

RNAi: an ever-growing puzzle

RNAi: an ever-growing puzzle

The four Rs of RNA-directed evolution

Evolutionary patterns of non-coding RNAs

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