The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription

Yang, Zhiyuan; Zhu, Qiangqiang; Luo, Kunxin; Zhou, Qiang

doi:10.1038/35104575

Cited by 635 publications

(655 citation statements)

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“…Examples include the steroid receptor RNA activator 58 , dsRNA motifs bound by the transcriptional regulator NF110 (ref. 59), the U1 small nuclear RNA that associates with TFIIH 60 and the 7SK RNA that inhibits Cdk9 (the RNA polymerase II C-terminal domain kinase) 61,62 . In these cases, coRNA seems to act as an allosteric effector.…”

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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Section: Rna-directed Dna Read-outmentioning

confidence: 99%

The four Rs of RNA-directed evolution

Herbert

2003

Nat Genet

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“…They are involved in several cellular activities such as gene silencing [53], replication [48], gene expression regulation [79], transcription [155], chromosome stability [9], protein stability [103], translocation [72] and localization [120] and RNA modification [88], processing [13] and stability [135]. New long antisense ncRNAs have been found in many genomes, that seem to be involved in gene expression regulation [65,98,113,114].…”

Section: Introductionmentioning

confidence: 99%

Computational methods in noncoding RNA research

2007

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Non protein-coding RNAs (ncRNAs) are a research hotspot in bioinformatics. Recent discoveries have revealed new ncRNA families performing a variety of roles, from gene expression regulation to catalytic activities. It is also believed that other families are still to be unveiled. Computational methods developed for protein coding genes often fail when searching for ncRNAs. Noncoding RNAs functionality is often heavily dependent on their secondary structure, which makes gene discovery very different from protein coding RNA genes. This motivated the development of specific methods for ncRNA research. This article reviews the main approaches used to identify ncRNAs and predict secondary structure.

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“…1,2 One of the key negative regulators of this process is the non-coding 7SK small nuclear RNA (snRNA) that inhibits the cyclindependant kinase P-TEFb (positive transcription elongation factor b). [3][4][5][6][7][8] 7SK sequesters P-TEFb by forming a ternary complex with the cyclin T1 subunit of P-TEFb and the HEXIM proteins. 9 The significance of this process is further highlighted by P-TEFb interactions with retroviral TAR (transactivation response region) RNA and Tat protein, which have evolved strategies to mimic the 7SK RNA and HEXIM protein, respectively.…”

Section: Introductionmentioning

confidence: 99%