NONHSAT113149

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Annotated Information

Name

7SK

Characteristics

~330 nt in vertebrates*. Transcribed by RNAP III, GC-rich sequence forming conserved secondary structures (especially 3' and 5' stem-loop motifs).

7SK RNA is capped at its 5' end by BCDIN3, a specific methylase methylphosphate capping enzyme (MePCE) ((Jeronimo 2007)).

RNAP II was recently found to bind near 7SK promoter, as well as many other known Pol III genes, suggesting that RNAP II may also play a role in regulating their transcription ((Raha 2010)).

In invertebrates, 7SK homologs may have different sizes (such as >400 nt and ~130 nt in drosophilids and nematodes, respectively). ((Gruber 2008)) ((Marz 2009))

Function

Controls RNAP II activity by inhibiting P-TEFb elongation factor, which is a cdk-cyclin kinase that functions as both a general and an HIV-1 Tat-specific transcription factor ((Nguyen 2001)) ((Yang 2001)), with an impact on cell growth and differentiation.

7SK snRNA is a central scaffold that coordinates protein-protein interactions and, by inhibiting P-TEFb kinase-mediated CTD phosphorylation, regulates RNAP II elongation ((Nguyen 2001)). 7SK snRNP (composed of 7SK snRNA, Hexim1, Larp7/Pip7S, and the P-TEFb subunits CycT1 and Cdk9) is not only critical for controlling transcription, but also for regulating alternative splicing coupled to transcription elongation ((Barboric 2009)). It is also essential for vertebrate development ((Barboric 2009)). The 3' end of HIC mRNA has full activity and contains a predicted structure resembling the 3'-terminal hairpin of 7SK that is critical for P-TEFb binding ((Barboric 2009)).

7SK has been found highly enriched in isolated chromatin fractions, which may be related to its role in transcriptional regulation ((Mondal 2010)).

At an early stage of the HIV transcription cycle, elongation is prevented as P-TEFb is recruited to the HIV-1 promoter in a catalytically inactive state bound to the 7SK snRNP and also the Tat trans-activator of transcription protein. The inhibitory 7SK snRNP may be displaced by the nascent TAR HIV RNA that also binds Tat protein, activating P-TEFb kinase and transcriptional elongation ((D'Orso 2010)). Displacement of 7SK may also be performed by cellular RNAs, as indicated by the 3'-untranslated region (~300-nt) of HIC mRNA, which forms complexes with P-TEFb and is necessary and sufficient for stimulation of P-TEFb-dependent transcription of the HIV promoter ((Young 2007)).

7SK RNA also inhibits APOBEC3C deaminase activity and sequesters it to the nucleolus, suggesting broader role for 7SK RNA in regulating key nuclear functions ((He 2007)).

Transcriptomic Nomeclature

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Regulation

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Expression

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Allelic Information and Variation

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Evolution

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Labs working on this lncRNA

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References

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Basic Information

Transcript ID	NONHSAT113149
Source	NONCODE4.0
Same with	,
Classification	intergenic
Length	332 nt
Genomic location	chr6+:52860418..52860749
Exon number	1
Exons	52860418..52860749
Genome context
Sequence	000001 GGATGTGAGG GCGATCTGGC TGCGACATCT GTCACCCCAT TGATCGCCAG GGTTGATTCG GCTGATCTGG CTGGCTAGGC 000080 000081 GGGTGTCCCC TTCCTCCCTC ACCGCTCCAT GTGCGTCCCT CCCGAAGCTG CGCGCTCGGT CGAAGAGGAC GACCATCCCC 000160 000161 GATAGAGGAG GACCGGTCTT CGGTCAAGGG TATACGAGTA GCTGCGCTCC CCTGCTAGAA CCTCCAAACA AGCTCTCAAG 000240 000241 GTCCATTTGT AGGAGAACGT AGGGTAGTCA AGCTTCCAAG ACTCCAGACA CATCCAAATG AGGCGCTGCA TGTGGCAGTC 000320 000321 TGCCTTTCTT TT

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Annotation (From lncRNAdb)

[NONHSAT113149]

Section	Description
ID	7SK
Characteristics	~330 nt in vertebrates*. Transcribed by RNAP III, GC-rich sequence forming conserved secondary structures (especially 3' and 5' stem-loop motifs). 7SK RNA is capped at its 5' end by BCDIN3, a specific methylase methylphosphate capping enzyme (MePCE) (Jeronimo (2007)). RNAP II was recently found to bind near 7SK promoter, as well as many other known Pol III genes, suggesting that RNAP II may also play a role in regulating their transcription (Raha (2010)). *In invertebrates, 7SK homologs may have different sizes (such as >400 nt and ~130 nt in drosophilids and nematodes, respectively). (Gruber (2008)) (Marz (2009))
Expression	Nuclear, highly abundant (one of the most abundant small RNAs in vertebrate cells), first isolated from HeLa nuclear extracts, but ubiquitously expressed. RNA sequencing from 11 humans tissues confirmed ubiquitous high expression of 7SK with expression in some tissues being higher than any mRNA (Castle (2010)).
Function	Controls RNAP II activity by inhibiting P-TEFb elongation factor, which is a cdk-cyclin kinase that functions as both a general and an HIV-1 Tat-specific transcription factor (Nguyen (2001)) (Yang (2001)), with an impact on cell growth and differentiation. 7SK snRNA is a central scaffold that coordinates protein-protein interactions and, by inhibiting P-TEFb kinase-mediated CTD phosphorylation, regulates RNAP II elongation (Nguyen (2001)). 7SK snRNP (composed of 7SK snRNA, Hexim1, Larp7/Pip7S, and the P-TEFb subunits CycT1 and Cdk9) is not only critical for controlling transcription, but also for regulating alternative splicing coupled to transcription elongation (Barboric (2009)). It is also essential for vertebrate development (Barboric (2009)). The 3' end of HIC mRNA has full activity and contains a predicted structure resembling the 3'-terminal hairpin of 7SK that is critical for P-TEFb binding (Barboric (2009)). 7SK has been found highly enriched in isolated chromatin fractions, which may be related to its role in transcriptional regulation (Mondal (2010)). At an early stage of the HIV transcription cycle, elongation is prevented as P-TEFb is recruited to the HIV-1 promoter in a catalytically inactive state bound to the 7SK snRNP and also the Tat trans-activator of transcription protein. The inhibitory 7SK snRNP may be displaced by the nascent TAR HIV RNA that also binds Tat protein, activating P-TEFb kinase and transcriptional elongation (D'Orso (2010)). Displacement of 7SK may also be performed by cellular RNAs, as indicated by the 3'-untranslated region (~300-nt) of HIC mRNA, which forms complexes with P-TEFb and is necessary and sufficient for stimulation of P-TEFb-dependent transcription of the HIV promoter (Young (2007)). 7SK RNA also inhibits APOBEC3C deaminase activity and sequesters it to the nucleolus, suggesting broader role for 7SK RNA in regulating key nuclear functions (He (2006)).
Conservation	Highly conserved throughout jawed vertebrates (but in lamprey it differs in 32% of its sequence from the mammalian 7SK (G®πrsoy (2000))), and has a few conserved sequence and structure motifs over longer evolutionary distances. Homologs have been identified in deuterostome invertebrates and in two protostome phyla (mollusks and annelids) (Gruber (2008)). More recently, it has also been detected in arthropods, showing that two highly structured conserved domains (5'- and 3'-stem regions) were present in the bilaterian ancestor (Gruber (2008)), and even in nematode Caenorhabditis species (Marz (2009)).
Misc	The 7SK family contains a number of pseudogenes and derived repeats. May be implicated in the transformation-dependent activation of oncogenes SV40 T-antigen and c-myc gene promoters (Krause (1996)).
Name	RN7SK: RNA, 7SK small nuclear

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