A hyperphosphorylated form of the large subunit of RNA polymerase II is associated with splicing complexes and the nuclear matrix.

Mortillaro, M; Blencowe, Benjamin J.; Wei, Xiangyun; Nakayasu, Hiroshi; Du, Lei; Warren, Stephen L.; Sharp, Phillip A.; Berezney, Ronald

doi:10.1073/pnas.93.16.8253

Cited by 298 publications

(248 citation statements)

References 35 publications

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“…Additionally, there is a need for new assays to probe the connections between promoter regulation and premRNA processing decisions. As RNA Pol II-RNA binding protein complexes may be reorganizing during mRNA synthesis, these data are consistent with models in which cotranscriptional assembly of RNPs is a dynamic process (Mortillaro et al 1996;Wetterberg et al 2001;Custodio et al 2004;Ujvari and Luse 2004;Yu et al 2004). …”

Section: Significance Of Genomic Localization Of Rna Binding Proteinssupporting

confidence: 73%

“…These early genomic efforts suggested that, similar to DNA binding proteins, functional groupings of genes are being bound by RNA binding proteins perhaps as post-transcriptional operons (Keene and Tenenbaum 2002). However, it is not known at which stage of RNA processing these operons are established.Much of pre-mRNA processing is coupled to transcription both physically and functionally, potentially through interactions with the C-terminal domain (CTD) of RNA polymerase II (RNA Pol II) (Mortillaro et al 1996;Yuryev et al 1996;Kim et al 1997). The CTD is phosphorylated as transcription begins.…”

mentioning

confidence: 99%

“…Much of pre-mRNA processing is coupled to transcription both physically and functionally, potentially through interactions with the C-terminal domain (CTD) of RNA polymerase II (RNA Pol II) (Mortillaro et al 1996;Yuryev et al 1996;Kim et al 1997). The CTD is phosphorylated as transcription begins.…”

mentioning

confidence: 99%

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Genomic localization of RNA binding proteins reveals links between pre-mRNA processing and transcription

Swinburne

Meyer²,

Liu³

et al. 2006

Genome Res.

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Pre-mRNA processing often occurs in coordination with transcription thereby coupling these two key regulatory events. As such, many proteins involved in mRNA processing associate with the transcriptional machinery and are in proximity to DNA. This proximity allows for the mapping of the genomic associations of RNA binding proteins by chromatin immunoprecipitation (ChIP) as a way of determining their sites of action on the encoded mRNA. Here, we used ChIP combined with high-density microarrays to localize on the human genome three functionally distinct RNA binding proteins: the splicing factor polypyrimidine tract binding protein (PTBP1/hnRNP I), the mRNA export factor THO complex subunit 4 (ALY/THOC4), and the 3Ј end cleavage stimulation factor 64 kDa (CSTF2). We observed interactions at promoters, internal exons, and 3Ј ends of active genes. PTBP1 had biases toward promoters and often coincided with RNA polymerase II (RNA Pol II). The 3Ј processing factor, CSTF2, had biases toward 3Ј ends but was also observed at promoters. The mRNA processing and export factor, ALY, mapped to some exons but predominantly localized to introns and did not coincide with RNA Pol II. Because the RNA binding proteins did not consistently coincide with RNA Pol II, the data support a processing mechanism driven by reorganization of transcription complexes as opposed to a scanning mechanism. In sum, we present the mapping in mammalian cells of RNA binding proteins across a portion of the genome that provides insight into the transcriptional assembly of RNA-protein complexes.[Supplemental material is available online at www.genome.org and http://silver.med.harvard.edu/brodsky/.] RNA binding proteins regulate many stages of RNA metabolism to help determine gene expression programs (for reviews, see Keene and Tenenbaum 2002;Hieronymus and Silver 2004). To prepare mRNA for export to and translation in the cytoplasm, many events including splicing, cleavage of the 3Ј end, and editing occur cotranscriptionally (Kornblihtt et al. 2004;Aguilera 2005a). After transcription, the mRNA-protein complex may reorganize as it is exported to the cytoplasm and prepared for translation (Fairman et al. 2004). Thus, significant efforts have been made to determine how RNA binding proteins interact at genes and/or mRNAs at various stages of mRNA metabolism (Tenenbaum et al. 2000;Brown et al. 2001;Hieronymus and Silver 2003;Ule et al. 2003;Yu et al. 2004). These early genomic efforts suggested that, similar to DNA binding proteins, functional groupings of genes are being bound by RNA binding proteins perhaps as post-transcriptional operons (Keene and Tenenbaum 2002). However, it is not known at which stage of RNA processing these operons are established.Much of pre-mRNA processing is coupled to transcription both physically and functionally, potentially through interactions with the C-terminal domain (CTD) of RNA polymerase II (RNA Pol II) (Mortillaro et al. 1996;Yuryev et al. 1996;Kim et al. 1997). The CTD is phosphorylated as transcription begins. Following...

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Section: Significance Of Genomic Localization Of Rna Binding Proteinssupporting

confidence: 73%

mentioning

confidence: 99%

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Genomic localization of RNA binding proteins reveals links between pre-mRNA processing and transcription

Swinburne

Meyer²,

Liu³

et al. 2006

Genome Res.

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“…For instance, the phospho-Ser2 CTD has been shown to interact with the Ser/Arg-rich (SR) proteins (e.g. SF2/ASF and SC35), Spt6, and snRNP particles (153)(154)(155)(156)(157). Providing visual support for this recruitment model, Pol II with the complete, but not a truncated CTD, was found to recruit splicing factors to sites of active transcription in living cells (158).…”

Section: Splicingmentioning

confidence: 93%

RNA Polymerase II Elongation Control

Peng¹,

Liu²,

Marion³

et al. 1998

Cold Spring Harbor Symposia on Quantitative Biology

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Regulation of the elongation phase of transcription by RNA Polymerase II (Pol II) is utilized extensively to generate the pattern of mRNAs needed to specify cell types and to respond to environmental changes. After Pol II initiates, negative elongation factors cause it to pause in a promoter proximal position. These polymerases are poised to respond to the positive transcription elongation factor, P-TEFb, and then enter productive elongation only under the appropriate set of signals to generate full length properly processed mRNAs. Recent global analyses of Pol II and elongation factors, mechanisms that regulate P-TEFb involving the 7SK snRNP, factors that control both the negative and positive elongation properties of Pol II and the mRNA processing events that are coupled with elongation are discussed.

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“…However, CTD might also play a role by providing a platform for the splicing machinery and even regulate the choice of alternative exons by increasing the local concentration of proteins (de la Mata and Kornblihtt, 2006). Splicing factors including small nuclear ribonucleoprotein particles (snRNPs) and non-snRNP proteins such as the serine/argininerich (SR) protein family are associated with pol IIo but not with pol IIa (Mortillaro et al, 1996;Kim et al, 1997). The arginine-serine rich (RS) domain of the SR family protein is essential for recruitment to the phosphorylated CTD (Misteli and Spector, 1999).…”

Section: Deciphering the Ctd Codementioning

confidence: 99%

RNA polymerase II carboxy-terminal domain with multiple connections

Cho¹

2007

Exp Mol Med

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The largest subunit of eukaryotic RNA polymerase II contains a unique domain at its carboxy-terminus, which is referred to as the carboxy-terminal domain (CTD). The CTD is made up of an evolutionarily conserved heptapeptide repeat (YSPTSPS). Over the past decade, there has been increasing attention on the role of the CTD in transcription regulation in the view of mRNA processing and chromatin remodeling. This paper provides a brief overview of the recent progress in the dynamic changes in CTD phosphorylation and its role in integrating multiple nuclear events.Keywords: carboxy-terminal domain kinase; chromatin; phosphorylation; histones; RNA polymerase II; RNA processing, post-transcriptional IntroductionThe largest subunit of eukaryotic RNA polymerase II (pol II) carboxy-terminal domain (CTD) consists of conserved heptapeptide repeats (Y 1 S 2 P 3 T 4 S 5 P 6 S 7 ) (Dahmus, 1996). Mammalian pol II CTD contains 52 repeats, whereas the yeast Saccharomyces cerevisiae CTD has 26-27. A deletion of the mouse, Drosophila, or yeast CTD is lethal. Therefore, the CTD is essential for the viability of an organism, even though the number of repeats can be reduced.Partial deletions of the CTD result in reduced transcription in vivo, and defective responses to various activators. The CTD acts as a platform to couple the mRNA metabolism and chromatin function to the transcription as it recruits various RNA processing/export and histone modifying factors to the transcription complex (Bentley, 2005;Buratowski, 2005;Phatnani and Greenleaf, 2006). This means that the CTD is very important for organizing various nuclear functions to acquire the proper regulation of gene expression. Those functions often depend on the CTD modification such as phosphorylation. Indeed, the CTD is rich in phosphoacceptor amino acid residues and undergoes reversible phosphorylation during the transcription cycle. Two forms of RNA pol II, which differ in the level of phosphorylation of the CTD, can be distinguished and are believed to have distinct functions in the transcription cycle; RNA pol IIa, with a hypophosphorylated CTD, is the form that assembles into the transcription initiation complexes, whereas pol IIo, with a hyperphosphorylated CTD is associated with the transcription elongation complexes. Phosphorylation occurs mainly at discrete serines (S) within the CTD repeats (S2, S5), which is then recognized by different proteins that interconnect the transcription to various nuclear metabolisms. Accordingly, serine phosphorylation is known as the 'CTD code', in a similar way that the 'histone code' refers to the histone modification (Buratowski, 2003). CTD with the phosphorylation codeEarlier models based on a two-step transcription cycle, in which pol IIa was assembled at the promoter and pol IIo carried out transcription elongation, have evolved to one with a more complex CTD phosphorylation cycle. Different modified forms of pol II dominate different stages of transcription (Komarnisky et al., 2000). Pol II assembled at the promoter is...

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A hyperphosphorylated form of the large subunit of RNA polymerase II is associated with splicing complexes and the nuclear matrix.

Cited by 298 publications

References 35 publications

Genomic localization of RNA binding proteins reveals links between pre-mRNA processing and transcription

Genomic localization of RNA binding proteins reveals links between pre-mRNA processing and transcription

RNA Polymerase II Elongation Control

RNA polymerase II carboxy-terminal domain with multiple connections

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