The Little Elongation Complex Regulates Small Nuclear RNA Transcription

Smith, Edwin R.; Lin, Chengqi; Garrett, Alexander S.; Thornton, Janet; Mohaghegh, Nima; Hu, Deqing; Jackson, Jessica; Saraf, Anita; Swanson, Selene K.; Seidel, Christopher; Florens, Laurence; Washburn, Michael P.; Eissenberg, Joel C.; Shilatifard, Ali

doi:10.1016/j.molcel.2011.12.008

Cited by 79 publications

(105 citation statements)

References 59 publications

(91 reference statements)

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“…In this case, any factor that is important for both transcription and 39-end processing will not be scored. This likely explains why depletion of members of the snRNA activating protein complex (SNAPc) do not trigger GFP expression, nor did the members of the recently defined Little Elongation Complex (Hung and Stumph 2011;Smith et al 2011). Depletion of any of these factors would be predicted to extinguish U7-GFP promoter activity and would not result in GFP expression.…”

Section: Discussionmentioning

confidence: 99%

An RNAi screen identifies additional members of the Drosophila Integrator complex and a requirement for cyclin C/Cdk8 in snRNA 3′-end formation

Chen¹,

Ezzeddine²,

Waltenspiel

et al. 2012

RNA

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Formation of the 39 end of RNA polymerase II-transcribed snRNAs requires a poorly understood group of proteins called the Integrator complex. Here we used a fluorescence-based read-through reporter that expresses GFP in response to snRNA misprocessing and performed a genome-wide RNAi screen in Drosophila S2 cells to identify novel factors required for snRNA 39-end formation. In addition to the known Integrator complex members, we identified Asunder and CG4785 as additional Integrator subunits. Functional and biochemical experiments revealed that Asunder and CG4785 are additional core members of the Integrator complex. We also identified a conserved requirement in both fly and human snRNA 39-end processing for cyclin C and Cdk8 that is distinct from their function in the Mediator Cdk8 module. Moreover, we observed biochemical association between Integrator proteins and cyclin C/Cdk8, and that overexpression of a kinase-dead Cdk8 causes snRNA misprocessing. These data functionally define the Drosophila Integrator complex and demonstrate an additional function for cyclin C/Cdk8 unrelated to its function in Mediator.

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Section: Discussionmentioning

confidence: 99%

An RNAi screen identifies additional members of the Drosophila Integrator complex and a requirement for cyclin C/Cdk8 in snRNA 3′-end formation

Chen¹,

Ezzeddine²,

Waltenspiel

et al. 2012

RNA

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“…Total RNA pol II (RPB1) ChIP-Seq data (reads and binding sites) were downloaded from NCBI GEO (GSE32120) 70 . Binding sites were annotated as described above.…”

Section: Methodsmentioning

confidence: 99%

dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes

et al. 2015

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dDsk2 is a conserved extraproteasomal ubiquitin receptor that targets ubiquitylated proteins for degradation. Here we report that dDsk2 plays a nonproteolytic function in transcription regulation. dDsk2 interacts with the dHP1c complex, localizes at promoters of developmental genes and is required for transcription. Through the ubiquitin-binding domain, dDsk2 interacts with H2Bub1, a modification that occurs at dHP1c complex-binding sites. H2Bub1 is not required for binding of the complex; however, dDsk2 depletion strongly reduces H2Bub1. Co-depletion of the H2Bub1 deubiquitylase dUbp8/Nonstop suppresses this reduction and rescues expression of target genes. RNA polymerase II is strongly paused at promoters of dHP1c complex target genes and dDsk2 depletion disrupts pausing. Altogether, these results suggest that dDsk2 prevents dUbp8/Nonstop-dependent H2Bub1 deubiquitylation at promoters of dHP1c complex target genes and regulates RNA polymerase II pausing. These results expand the catalogue of nonproteolytic functions of ubiquitin receptors to the epigenetic regulation of chromatin modifications.

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“…It has been reported that two ELL/EAF-containing complexes, super elongation complex (SEC) and little elongation complex (LEC), specifically regulate the transcription of distinct genes [4,5]. LEC is composed of multiple subunits including the ELL/EAF component, KIAA0947, NARG2 and ZC3H8 [3,6,7].…”

Section: Transcription Elongation Factors Including Eleven Lysine-ricmentioning

confidence: 99%

“…LEC is composed of multiple subunits including the ELL/EAF component, KIAA0947, NARG2 and ZC3H8 [3,6,7]. KIAA0947 and NARG2 were also known as ICE1 and ICE2 (interacts with C-terminus of ELL subunits 1 and 2), respectively [4]. It has been shown that LEC plays an essential role in transcription of small nuclear RNA (snRNA) genes.…”

Section: Transcription Elongation Factors Including Eleven Lysine-ricmentioning

confidence: 99%

p53 represses the transcription of snRNA genes by preventing the formation of little elongation complex

Anwar

Takahashi

Watanabe

et al. 2016

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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The Little Elongation Complex Regulates Small Nuclear RNA Transcription

Cited by 79 publications

References 59 publications

An RNAi screen identifies additional members of the Drosophila Integrator complex and a requirement for cyclin C/Cdk8 in snRNA 3′-end formation

An RNAi screen identifies additional members of the Drosophila Integrator complex and a requirement for cyclin C/Cdk8 in snRNA 3′-end formation

dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes

p53 represses the transcription of snRNA genes by preventing the formation of little elongation complex

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