7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes

Nguyen, Van Toan; Kiss, Tamás; Michels, Annemieke A.; Bensaude, Olivier

doi:10.1038/35104581

Cited by 638 publications

(695 citation statements)

References 25 publications

Supporting

Mentioning

653

Contrasting

Unclassified

Order By: Relevance

“…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

View full text Add to dashboard Cite

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...

show abstract

Section: Rna-directed Dna Read-outmentioning

confidence: 99%

The four Rs of RNA-directed evolution

Herbert

2003

Nat Genet

View full text Add to dashboard Cite

show abstract

“…Its sequence is conserved between mouse and human (Blencowe 2002). 7SK function was revealed by the discovery that the RNA bound to and inhibited the RNA pol II transcription elongation factor P-TEFb, which consists of a CDK9-cyclin T1 or T2 or K heterodimer (Nguyen et al 2001;Yang et al 2001). 7SK also interacts with HEXIM1/2, which together with P-TEFb forms the inactive P-TEFb complex that cannot engage in the transcriptional elongation-dependent phosphorylation of the CTD of RNA pol II (Yik et al 2003(Yik et al , 2004Michels et al 2004).…”

Section: Sk Rnamentioning

confidence: 99%

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

Prasanth¹,

Spector²

2007

Genes Dev.

363

305

View full text Add to dashboard Cite

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.

show abstract

“…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%