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      Dynamics of the RNA polymerase I TFIIF/TFIIE-like subcomplex: a mini-review

      1 , 2 , 2
      Biochemical Society Transactions
      Portland Press Ltd.

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          Abstract

          RNA polymerase I (Pol I) is the most specialized eukaryotic Pol. It is only responsible for the synthesis of pre-ribosomal RNA (rRNA), the precursor of 18S, 5.8S and 28S rRNA, the most abundant cellular RNA types. Aberrant Pol I transcription is observed in a wide variety of cancers and its down-regulation is associated with several genetic disorders. The regulation and mechanism of Pol I transcription is increasing in clarity given the numerous high-resolution Pol I structures that have helped bridge seminal genetic and biochemical findings in the field. Here, we review the multifunctional roles of an important TFIIF- and TFIIE-like subcomplex composed of the Pol I subunits A34.5 and A49 in yeast, and PAF49 and PAF53 in mammals. Recent analyses have revealed a dynamic interplay between this subcomplex at nearly every step of the Pol I transcription cycle in addition to new roles in chromatin traversal and the existence of a new helix-turn-helix (HTH) within the A49/PAF53 linker domain that expands its dynamic functions during the Pol I transcription process.

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          Structure of activated transcription complex Pol II–DSIF–PAF–SPT6

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            Architecture of the RNA polymerase II-Mediator core initiation complex.

            The conserved co-activator complex Mediator enables regulated transcription initiation by RNA polymerase (Pol) II. Here we reconstitute an active 15-subunit core Mediator (cMed) comprising all essential Mediator subunits from Saccharomyces cerevisiae. The cryo-electron microscopic structure of cMed bound to a core initiation complex was determined at 9.7 Å resolution. cMed binds Pol II around the Rpb4-Rpb7 stalk near the carboxy-terminal domain (CTD). The Mediator head module binds the Pol II dock and the TFIIB ribbon and stabilizes the initiation complex. The Mediator middle module extends to the Pol II foot with a 'plank' that may influence polymerase conformation. The Mediator subunit Med14 forms a 'beam' between the head and middle modules and connects to the tail module that is predicted to bind transcription activators located on upstream DNA. The Mediator 'arm' and 'hook' domains contribute to a 'cradle' that may position the CTD and TFIIH kinase to stimulate Pol II phosphorylation.
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              Structure of eukaryotic RNA polymerases.

              The eukaryotic RNA polymerases Pol I, Pol II, and Pol III are the central multiprotein machines that synthesize ribosomal, messenger, and transfer RNA, respectively. Here we provide a catalog of available structural information for these three enzymes. Most structural data have been accumulated for Pol II and its functional complexes. These studies have provided insights into many aspects of the transcription mechanism, including initiation at promoter DNA, elongation of the mRNA chain, tunability of the polymerase active site, which supports RNA synthesis and cleavage, and the response of Pol II to DNA lesions. Detailed structural studies of Pol I and Pol III were reported recently and showed that the active center region and core enzymes are similar to Pol II and that strong structural differences on the surfaces account for gene class-specific functions.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Biochemical Society Transactions
                Portland Press Ltd.
                0300-5127
                1470-8752
                October 30 2020
                September 11 2020
                October 30 2020
                September 11 2020
                : 48
                : 5
                : 1917-1927
                Affiliations
                [1 ]Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, U.S.A.
                [2 ]Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, U.S.A.
                Article
                10.1042/BST20190848
                32915199
                d960ab30-228c-448c-a660-e7907d0112f8
                © 2020
                History

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