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      A novel TBP-TAF complex on RNA Polymerase II-transcribed snRNA genes

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          Abstract

          Initiation of transcription of most human genes transcribed by RNA polymerase II (RNAP II) requires the formation of a preinitiation complex comprising TFIIA, B, D, E, F, H and RNAP II. The general transcription factor TFIID is composed of the TATA-binding protein and up to 13 TBP-associated factors. During transcription of snRNA genes, RNAP II does not appear to make the transition to long-range productive elongation, as happens during transcription of protein-coding genes. In addition, recognition of the snRNA gene-type specific 3′ box RNA processing element requires initiation from an snRNA gene promoter. These characteristics may, at least in part, be driven by factors recruited to the promoter. For example, differences in the complement of TAFs might result in differential recruitment of elongation and RNA processing factors. As precedent, it already has been shown that the promoters of some protein-coding genes do not recruit all the TAFs found in TFIID. Although TAF5 has been shown to be associated with RNAP II-transcribed snRNA genes, the full complement of TAFs associated with these genes has remained unclear. Here we show, using a ChIP and siRNA-mediated approach, that the TBP/TAF complex on snRNA genes differs from that found on protein-coding genes. Interestingly, the largest TAF, TAF1, and the core TAFs, TAF10 and TAF4, are not detected on snRNA genes. We propose that this snRNA gene-specific TAF subset plays a key role in gene type-specific control of expression.

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          Most cited references73

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          The general transcription machinery and general cofactors.

          In eukaryotes, the core promoter serves as a platform for the assembly of transcription preinitiation complex (PIC) that includes TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH, and RNA polymerase II (pol II), which function collectively to specify the transcription start site. PIC formation usually begins with TFIID binding to the TATA box, initiator, and/or downstream promoter element (DPE) found in most core promoters, followed by the entry of other general transcription factors (GTFs) and pol II through either a sequential assembly or a preassembled pol II holoenzyme pathway. Formation of this promoter-bound complex is sufficient for a basal level of transcription. However, for activator-dependent (or regulated) transcription, general cofactors are often required to transmit regulatory signals between gene-specific activators and the general transcription machinery. Three classes of general cofactors, including TBP-associated factors (TAFs), Mediator, and upstream stimulatory activity (USA)-derived positive cofactors (PC1/PARP-1, PC2, PC3/DNA topoisomerase I, and PC4) and negative cofactor 1 (NC1/HMGB1), normally function independently or in combination to fine-tune the promoter activity in a gene-specific or cell-type-specific manner. In addition, other cofactors, such as TAF1, BTAF1, and negative cofactor 2 (NC2), can also modulate TBP or TFIID binding to the core promoter. In general, these cofactors are capable of repressing basal transcription when activators are absent and stimulating transcription in the presence of activators. Here we review the roles of these cofactors and GTFs, as well as TBP-related factors (TRFs), TAF-containing complexes (TFTC, SAGA, SLIK/SALSA, STAGA, and PRC1) and TAF variants, in pol II-mediated transcription, with emphasis on the events occurring after the chromatin has been remodeled but prior to the formation of the first phosphodiester bond.
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            Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II.

            The C-terminal domain (CTD) of RNA polymerase II (RNAPII) is an essential component of transcriptional regulation and RNA processing of protein-coding genes. A large body of data also implicates the CTD in the transcription and processing of RNAPII-mediated small nuclear RNAs (snRNAs). However, the identity of the complex (or complexes) that associates with the CTD and mediates the processing of snRNAs has remained elusive. Here, we describe an RNA polymerase II complex that contains at least 12 novel subunits, termed the Integrator, in addition to core RNAPII subunits. Two of the Integrator subunits display similarities to the subunits of the cleavage and polyadenylation specificity factor (CPSF) complex. We show that Integrator is recruited to the U1 and U2 snRNA genes and mediates the snRNAs' 3' end processing. The Integrator complex is evolutionarily conserved in metazoans and directly interacts with the C-terminal domain of the RNA polymerase II largest subunit.
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              The role of general initiation factors in transcription by RNA polymerase II.

              R Roeder (1996)
              Transcription initiation on protein-encoding genes represents a major control point for gene expression in eukaryotes, and is mediated by RNA polymerase II and a surprisingly complex array of general initiation factors (TFIIA, -B, -D, -E, -F and -H) that are highly conserved from yeast to man. Elucidation of structural and functional features of these factors on model promoters has revealed insights into biochemical mechanisms and provides a basis for understanding their regulation on diverse promoters by gene- and cell-specific activators.
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                Author and article information

                Journal
                Transcription
                Transcription
                TRNS
                Transcription
                Landes Bioscience
                2154-1264
                2154-1272
                01 March 2012
                01 March 2012
                : 3
                : 2
                : 92-104
                Affiliations
                [1 ]Sir William Dunn School of Pathology; University of Oxford; Oxford, UK
                [2 ]Laboratory of Biochemistry and Molecular Biology; The Rockefeller University; New York, NY USA
                Author notes
                [* ]Correspondence to: Shona Murphy, Email: shona.murphy@ 123456path.ox.ac.uk
                Article
                2012TRANS0007R 19783
                10.4161/trns.19783
                3337830
                22441827
                a441954a-8603-4d41-8b59-eb6dc1e01461
                Copyright © 2012 Landes Bioscience

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

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                Categories
                Research Paper

                Molecular biology
                gene regulation,pre-initiation complex,tfiid,snrna genes,tafs
                Molecular biology
                gene regulation, pre-initiation complex, tfiid, snrna genes, tafs

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