Transcription by Odd Pols

TY - JOUR

T1 - Transcription by Odd Pols

AU - Bhargava, Purnima

AU - Reese, Joseph C.

N1 - Funding Information: Purnima Bhargava ⁎ [email protected] Joseph C. Reese Center for Cellular and Molecular Biology, Eukaryotic Transcription Lab, Uppal Road, Tarnaka, Hyderabad, Andhra Pradesh 500 007, India Center for Eukaryotic Gene Regulation, The Pennsylvania State University, United States ⁎ Corresponding author. Tel.: + 91 40 27192603; fax: + 91 40 27160591. RNA polymerases (Pols) I and III of eukaryotes, popularly known as “Odd Pols” are comparatively more complex and more efficient than their “even” counterpart, RNA polymerase II. Though a larger fraction of the genome is transcribed by Pol II, Odd Pols are responsible for 70–80% of the cellular transcription activity. Yet, the vast majority of all effort to research transcription by eukaryotic RNA polymerases has been dedicated to the mechanisms used by RNA polymerase II. However, renewed interest in Odd Pols appears to be reversing this trend. It is now widely accepted that Pol I and Pol III transcription, processes once thought to be constitutive, is subject to as fascinating forms of regulation as their better studied counterpart, Pol II. Several labs have reported many new and interesting findings in Odd Pol transcription field and this special issue provides a comprehensive overview of the field. Journey of Odd Pol research commenced many years back along with Pol II research. Michel Riva and Andre Sentenac chronicle the exciting discoveries throughout the years, providing a nostalgic view of how the field thrived on the sheer hard work and dedication of its researchers. The groundwork laid during the earlier days made it possible to prepare highly purified polymerases in sufficient quantities to solve X-ray structure of their crystals, which revealed that all three RNA polymerases are strikingly similar at core. Alessandro Vannini provides a structural perspective on the current understanding of the molecular mechanisms of RNA synthesis by Odd Pols and their regulatory factors. It is not surprising that, similar to the polymerases, even the core general transcription factors (GTF) for each polymerase have structurally similar domains. BRF, the TFIIB related factor used by Pol III, has been known for a long time now. The missing TFIIB-like factor in the Pol I system was not known for many years. Bruce Knutson gives an account of the recently discovered TFIIB-related factors used by Pol I. We may soon learn that similar to TFIIB, its counterparts for the Odd Pols also help decide the point of transcription initiation via a similar mechanism. Two articles in this collection provide thorough reviews on the general transcription factors and effectors of Pol III. Transcription factor TFIIIA, which plays a unique role in 5S DNA transcription by Pol III, was also the first identified zinc-finger protein. The subject of intense research for a long time, interest in this protein waned as researchers turned their attention to other proteins regulating Pol II transcription. However, new developments have renewed interest in TFIIIA, including its interaction with optineurin, the protein encoded by a gene associated with the eye disease glaucoma. Sylvette Tourmente gives an update on its structure, function and regulation. TFIIIC and B are reviewed by Olivier Lefebvre and colleagues, who also give a list of other Pol III effectors, especially in yeast. This, and other reviews in the collection, calls attention to an emerging theme: many regulators of Pol I and Pol III transcription also function in Pol II transcription. The sharing of these factors between different Pols is in line with the current popular thought that much of the intracellular co-ordination of cellular physiology could be via common regulators modulating transcription of all the three polymerases. The three polymerases may share subunits and utilize a common set of factors, but their target genes are distinct. Ribosomal DNA sequences, Pol II-transcribed open reading frames and Pol III-transcribed non-coding genes are annotated in databases according to set rules. However, Pol III transcriptome appears to be ever expanding, redefining previously accepted methodologies to define their transcription units. Giorgio Dieci and colleagues discuss the newly identified Pol III targets as well as tools to annotate them in the genomes of eukaryotes. The transcription initiation and elongation steps by all three polymerases have received the attention of many scientists. Interest has been building on the termination process of pols in the last few years especially termination of Pol I and Pol II. The process has been comparatively better studied for pol III. Reviews of the Pol III termination process by Richard Maraia and another by Giorgio Dieci cover the final stages of transcription and account for the entire transcription cycle of Pol III by linking initiation with termination. Furthermore, Herbert Tschochner and colleagues summarize the latest advances in understanding Pol I termination and make the case that its complexity matches that of Pol II. Both Pol I and Pol III were once thought to be constitutively active. However, we now know that the activity of Odd Pols is curtailed under stress conditions, suggesting they are meticulously regulated nonetheless. We are just starting to define the factors and mechanisms that exert this level of control. Maf1, a likely downstream receptor of stress signals, has been considered a master regulator of Pol III transcription. Its central importance is highlighted by two reviews by Ian Willis and Magdalena Boguta. Both elucidate possible mechanisms and models for Maf1 action, based on the current knowledge generated in both yeast and metazoan systems. Retinoblastoma (RB) protein and p53 are two known Pol III regulators, which are hypothesized to regulate Pol III activity during the cell cycle and under stress. Elaborating on the distribution profile of RB on mammalian Pol III targets, Alison Gjidoda and William Henry suggest involvement of chromatin-related mechanisms in regulating Pol III transcription during tumorigenesis. It is not only Pol III that is dysregulated during cancer. Ross Hannan and colleagues provide a highly informative review article describing the connections between Pol I and human diseases and a variety of ribosomopathies. They elaborate on not only the molecular mechanisms of such disorders, but also provide provocative ideas for therapeutic intervention. It is well established that chromatin has profound influences on Pol II transcription. However, the same could not be said of Odd Pol transcription due to a lack of sufficient number of studies. In fact, some theorized that rDNA and tRNAs are nucleosome “free” due to their high rates of transcription. This simplified view has been challenged by a number of important discoveries. Ingrid Grummt and Gernot Langst have reviewed epigenetic phenomena associated with rDNA transcription while Joachim Griesenbeck and colleagues have focused on structural aspects of chromatin states on active/silent rDNA copies. Pol III-transcribed genes and their factor TFIIIC have been attributed genome-organizing properties. Rohinton Kamakaka and colleagues review the recent advances in this direction, which illuminate how the barrier and insulator activities of TFIIIC and tDNAs affect chromatin structure and gene activity. We hope that this special issue serves as a critical resource for those working on Odd Pols and calls attention to the fascinating new developments to those outside of the field. We predict that the Odd Pol research is going to see a transformation in near future as novel and unexpected findings continue to be made. Joseph Reese is a Professor of Biochemistry and Molecular Biology and member of the Center for Eukaryotic Gene Regulation at The Pennsylvania State University. He obtained his Ph.D. from the University of Illinois, Urbana-Champaign, working on the molecular actions of estrogen agonists and antagonists. He was a postdoctoral fellow of the Damon Runyon–Walter Winchell Cancer Research Fund at the University of Massachusetts Medical Center where he identified and characterized TBP-associated factors from budding yeast. His research interests are in the mechanisms of chromatin remodeling and gene transcription and his current work is on the regulation of DNA damage induced genes in yeast. His work on the ribonucleotide reductase genes has revealed mechanisms of co-repressor actions and provided the first description of a role for the general transcription machinery, especially TFII;D, in the remodeling of chromatin at promoters. He has served on multiple study sections at the National Institutes of Health, the American Cancer Society, and the American Heart Association and currently serves on two Editorial Boards, including his role as Executive Editor of BBA Gene Regulatory Mechanisms . Purnima Bhargava had her Masters in Biochemistry and obtained her Ph.D. in Neurochemistry from Banaras Hindu University, India in 1983. As a Chief Scientist at the Centre for Cellular & Molecular Biology, Hyderabad, India, her research interests are focused on the epigenetic mechanisms of gene regulation. In the early nineties, she showed that some transient, conformational changes in a nucleosome can take place to make read-through by an elongating RNA pol II possible, without losing the histone octamer. Her major research contributions in recent years have been the elucidation of several novel mechanisms exploited by the yeast SNR6 (U6snRNA) gene, for its transcriptional activation, both in vivo and in vitro, wherein the transcription factor IIIC, a basal factor for the enzyme RNA polymerase III, also works as an activator by recruiting a chromatin remodeling factor to the gene. She had earlier shown that during the very early steps of transcription initiation, unlike other RNA polymerases, almost all of yeast RNA polymerase III molecules escape the abortive phase without significant pausing or arrest. Her work on the mechanisms of nucleosome positioning on the genes has helped to understand the role of a sequence-specific DNA-binding protein in maintaining chromatin structure. She has been elected Fellow of the National Academy of Sciences, India and Indian Academy of Sciences.

PY - 2013/3

Y1 - 2013/3

UR - http://www.scopus.com/inward/record.url?scp=84875249522&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875249522&partnerID=8YFLogxK

U2 - 10.1016/j.bbagrm.2013.02.001

DO - 10.1016/j.bbagrm.2013.02.001

M3 - Editorial

C2 - 23411050

AN - SCOPUS:84875249522

SN - 1874-9399

VL - 1829

SP - 249

EP - 250

JO - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms

JF - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms

IS - 3-4

ER -