Transcription control by long non-coding RNAs

Faust, Thomas W.; Frankel, Alan D.; D’Orso, Iván

doi:10.4161/trns.19349

Cited by 23 publications

(17 citation statements)

References 98 publications

(100 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro systems will be required to more precisely define the kinetics of assembly and displacement of these factors and the activity of the P-TEFb kinase alone, bound to Tat, and in the context of the Tat:7SK snRNP complex (38,45,79,101,110,119). In apparent disagreement with our model, a previous observation that P-TEFb is easily extracted from chromatin with high-salt treatment (6) suggested that 7SK snRNP complexes do not stably associate with chromatin (76,78); however, recent genome-wide experiments examining the assembly of noncoding RNAs with chromatin demonstrated that 7SK snRNA is enriched several thousandfold in the chromatin fraction (69), raising the possibility that 7SK complexes selectively assemble at specific promoters (28).…”

Section: Discussioncontrasting

confidence: 54%

Transition Step during Assembly of HIV Tat:P-TEFb Transcription Complexes and Transfer to TAR RNA

D’Orso

Jang

Pastuszak

et al. 2012

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

bTranscription factors regulate eukaryotic RNA polymerase II (Pol II) activity by assembling and remodeling complexes at multiple steps in the transcription cycle. In HIV, we previously proposed a two-step model where the viral Tat protein first preassembles at the promoter with an inactive P-TEFb:7SK snRNP complex and later transfers P-TEFb to TAR on the nascent transcript, displacing the inhibitory snRNP and resulting in Pol II phosphorylation and stimulation of elongation. It is unknown how the Tat:P-TEFb complex transitions to TAR to activate the P-TEFb kinase. Here, we show that P-TEFb artificially recruited to the nascent transcript is not competent for transcription but rather remains inactive due to its assembly with the 7SK snRNP. Tat supplied in trans is able to displace the kinase inhibitor Hexim1 from the snRNP and activate P-TEFb, thereby uncoupling Tat requirements for kinase activation and TAR binding. By combining comprehensive mutagenesis of Tat with multiple cellbased reporter assays that probe the activity of Tat in different arrangements, we genetically defined a transition step in which preassembled Tat:P-TEFb complexes switch to TAR. We propose that a conserved network of residues in Tat has evolved to control this transition and thereby switch the host elongation machinery to viral transcription.

show abstract

Section: Discussioncontrasting

confidence: 54%

Transition Step during Assembly of HIV Tat:P-TEFb Transcription Complexes and Transfer to TAR RNA

D’Orso

Jang

Pastuszak

et al. 2012

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Transcriptional pausing is a well-known phenomenon, where RNA polymerase II (RNAPII) becomes trapped downstream of the transcriptional start site (TSS) and is unable to escape into productive elongation [148]. P-TEFb, the positive transcription elongation factor, plays an essential role in facilitating RNAPII escape from this paused state.…”

Section: Regulatory Functions Of Lncrnas and Mrnasmentioning

confidence: 99%

“…P-TEFb, the positive transcription elongation factor, plays an essential role in facilitating RNAPII escape from this paused state. When recruited to promoters, P-TEFb phosphorylates the C -terminal domain (CTD) of RNAPII, allowing the escape into productive elongation [148]. In vivo , P-TEFb is present in two states: an active P-TEFb form, associated with Brd4 and other factors, and in an inactive ribonucleoprotein from, referred to as 7SK snRNP, containing a 331-nt non-coding RNA known as 7SK snRNA.…”

Section: Regulatory Functions Of Lncrnas and Mrnasmentioning

confidence: 99%

“…In vivo , P-TEFb is present in two states: an active P-TEFb form, associated with Brd4 and other factors, and in an inactive ribonucleoprotein from, referred to as 7SK snRNP, containing a 331-nt non-coding RNA known as 7SK snRNA. RNase footprinting and mutagenesis experiments have indicated that 7SK contains a high degree of secondary structure, with stem-loops at both the 5' and 3' ends [96,148,149,150]. The 5' stem loop binds P-TEFb as well as the Hexim1 protein, which acts to inhibit the kinase activity, while the 3' stem-loop binds the Larp7/PIP7S protein, which, in addition to a methylphosphate capping enzyme (Mepce), stabilizes the RNA [95,96,97,98,99,151,152].…”

Section: Regulatory Functions Of Lncrnas and Mrnasmentioning

confidence: 99%

See 1 more Smart Citation

Regulatory Roles for Long ncRNA and mRNA

Karapetyan

Buiting

Kuiper

et al. 2013

Cancers

View full text Add to dashboard Cite

Recent advances in high-throughput sequencing technology have identified the transcription of a much larger portion of the genome than previously anticipated. Especially in the context of cancer it has become clear that aberrant transcription of both protein-coding and long non-coding RNAs (lncRNAs) are frequent events. The current dogma of RNA function describes mRNA to be responsible for the synthesis of proteins, whereas non-coding RNA can have regulatory or epigenetic functions. However, this distinction between protein coding and regulatory ability of transcripts may not be that strict. Here, we review the increasing body of evidence for the existence of multifunctional RNAs that have both protein-coding and trans-regulatory roles. Moreover, we demonstrate that coding transcripts bind to components of the Polycomb Repressor Complex 2 (PRC2) with similar affinities as non-coding transcripts, revealing potential epigenetic regulation by mRNAs. We hypothesize that studies on the regulatory ability of disease-associated mRNAs will form an important new field of research.

show abstract

“…13,14 Although initially argued to be spurious transcriptional noise, recent evidence suggests that the proverbial 'dark matter' of the genome may has a major biological role in cellular development, differentiation and metabolism. 15 The small number of characterized human lncRNAs have been associated with a spectrum of biological processes including epigenetics, alternative splicing, nuclear import, as structural components, as precursors to small RNAs and even as regulators of mRNA decay, [16][17][18][19][20][21] every level of the gene expression program (Figure 1). Furthermore, accumulating reports of misregulated lncRNA expression across numerous cancer types suggest that aberrant lncRNA expression may be a major contributor to tumorigenesis.…”

mentioning

confidence: 99%

The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine

2013

View full text Add to dashboard Cite

The conventional view of gene regulation in biology has centered around protein-coding genes via the central dogma of DNA-mRNA-protein. The discovery of thousands of long non-coding RNAs (lncRNAs) has certainly changed our view of the complexity of mammalian genomes and transcriptomes, as well as many other aspects of biology including transcriptional and posttranscriptional regulation of gene expression. Accumulating reports of misregulated lncRNA expression across numerous cancer types suggest that aberrant lncRNA expression may be a major contributor to tumorigenesis. Here, we summarize recent data about the biological characteristics of lncRNAs in cancer pathways. These include examples with a wide range of molecular mechanisms involved in gene regulation. We also consider the medical implications, and discuss how lncRNAs can be used for cancer diagnosis and prognosis, and serve as potential therapeutic targets. As more examples of regulation by lncRNA are uncovered, one might predict that the large transcripts will eventually rival small RNAs and proteins in their versatility as regulators of genetic information.

show abstract

Transcription control by long non-coding RNAs

Cited by 23 publications

References 98 publications

Transition Step during Assembly of HIV Tat:P-TEFb Transcription Complexes and Transfer to TAR RNA

Transition Step during Assembly of HIV Tat:P-TEFb Transcription Complexes and Transfer to TAR RNA

Regulatory Roles for Long ncRNA and mRNA

The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine

Contact Info

Product

Resources

About