An RNA Polymerase II Promoter in the <i>hsp70</i> Locus of <i>Trypanosoma brucei</i>

Lee, Mary Gwo-Shu

doi:10.1128/mcb.16.3.1220

Cited by 48 publications

(32 citation statements)

References 50 publications

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“…A pol II promoter for the spliced leader (SL) array has been characterized (61). There have also been reports that sequences from actin (13) and HSP70 (99) loci can act as promoters when placed upstream of exogenous reporter genes. However, it was not clear that either putative promoter was a true pol II initiation site in its endogenous position, and in subsequent analyses neither sequence gave significant activity (120).…”

Section: Rna Polymerase II Transcription Unitsmentioning

confidence: 99%

Cell Biology of the Trypanosome Genome

Daniels

Gull

Wickstead

2010

Microbiol Mol Biol Rev

113

103

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SUMMARY Trypanosomes are a group of protozoan eukaryotes, many of which are major parasites of humans and livestock. The genomes of trypanosomes and their modes of gene expression differ in several important aspects from those of other eukaryotic model organisms. Protein-coding genes are organized in large directional gene clusters on a genome-wide scale, and their polycistronic transcription is not generally regulated at initiation. Transcripts from these polycistrons are processed by global trans-splicing of pre-mRNA. Furthermore, in African trypanosomes, some protein-coding genes are transcribed by a multifunctional RNA polymerase I from a specialized extranucleolar compartment. The primary DNA sequence of the trypanosome genomes and their cellular organization have usually been treated as separate entities. However, it is becoming increasingly clear that in order to understand how a genome functions in a living cell, we will need to unravel how the one-dimensional genomic sequence and its trans-acting factors are arranged in the three-dimensional space of the eukaryotic nucleus. Understanding this cell biology of the genome will be crucial if we are to elucidate the genetic control mechanisms of parasitism. Here, we integrate the concepts of nuclear architecture, deduced largely from studies of yeast and mammalian nuclei, with recent developments in our knowledge of the trypanosome genome, gene expression, and nuclear organization. We also compare this nuclear organization to those in other systems in order to shed light on the evolution of nuclear architecture in eukaryotes.

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Section: Rna Polymerase II Transcription Unitsmentioning

confidence: 99%

Cell Biology of the Trypanosome Genome

Daniels

Gull

Wickstead

2010

Microbiol Mol Biol Rev

113

103

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“…In addition, RNA polymerase II promoters have been difficult to detect in trypanosomes. Two putative promoter regions were described as transcriptionally void regions upstream from the highly transcribed actin and Hsp70 genes (22,23). However, one example of RNA polymerase II promoter was recently identified in the spliced leader genes of the parasite Leptomonas seymouri (24).…”

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confidence: 99%

TcUBP-1, a Developmentally Regulated U-rich RNA-binding Protein Involved in Selective mRNA Destabilization in Trypanosomes

D’Orso¹,

Frasch

2001

Journal of Biological Chemistry

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Developmental stages of the trypanosome life cycle differ in their morphology, biology, and biochemical properties. Consequently, several proteins have to be tightly regulated in their expression to allow trypanosomes to adapt rapidly to sudden environmental changes, a process that might be of central importance for parasite survival. However, in contrast to higher eukaryotic cells, trypanosomes do not seem to regulate gene expression through regulation of transcription initiation. These parasites make use of post-transcriptional regulatory mechanisms and modification of mRNA halflife is a relevant one. Trans-acting factors binding to cis-elements that affect mRNA stability of mature transcripts have not been identified in these cells. In this work, a novel U-rich RNA-binding protein (TcUBP-1) from Trypanosoma cruzi, the agent of Chagas disease, was identified. Its structure includes an RNA recognition motif, a nuclear export signal, and auxiliary domains with glycine-and glutamine-rich regions. Messenger RNA degradation/stabilization is one of the mechanisms that control gene expression in higher eukaryotic cells (1). One well characterized cis-element that regulates mRNA stability is an AU-rich element (ARE) 1 found in the 3ЈUTR of short-lived mRNAs (2, 3) such as those of proto-oncogenes and cytokines (interleukin-1, -2, -3, and -10) (4 -6). Each ARE represents a combination of functionally and structurally distinct sequence motifs such as the AUUUA pentamer, the UUAUUUA(U/A)(U/A) nonamer, and stretches of uridines and/or U-rich domains that range in size from 50 to 150 bp. It was shown that ARE-directed mRNA decay is linked to cell transformation, cell growth and differentiation, cell adhesion, and immune response regulation (7). An effect of the ARE on translation efficiency was also described both positively (8) and negatively (9). RNA-binding proteins that exhibit affinity for, and interact with, ARE sequences have been identified in higher eukaryotes. Many of these factors contain highly conserved RNA binding domains that place them within RNA recognition motif (RRM) superfamily (10). Two kinds of transacting factors were described that have opposite functions. The ELAV protein HuR increases stability of ARE-containing mRNAs when over-expressed in transfected fibroblasts (11). Conversely, AUF-1/hnRNP D (12) mediates a destabilizing activity of the mRNAs containing ARE sequences within their 3ЈUTR (13). It was proposed that ELAV proteins may bind the ARE-containing mRNAs in the nucleus and transport them to the cytoplasm, where they either find access to the translational apparatus or are released for rapid degradation (14).Other hnRNPs, such as hnRNP A1 and C (15), hnRNP A0 (16), and some RNA-binding proteins displaying catalytic activities such as glyceraldehyde-3-phosphate-dehydrogenase (17), AUH, an enoyl-CoA hydratase (18), were also shown to be AU-rich RNA-binding proteins. Trypanosomes, protozoan parasites from the order Kinetoplastida, cause widespread diseases in humans, domestic animals, and w...

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“…Transcriptional start sites for primary mRNAs have been extremely difficult to detect. Two putative promoter regions were tentatively defined as transcriptionally void regions upstream from the highly transcribed actin and HSP 70 genes (12,13). However, placement of these sequences upstream from a luciferase coding region did not yield even modest levels of reporter gene activity (14).…”

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confidence: 99%

Transcription Initiation at the TATA-less Spliced Leader RNA Gene Promoter Requires at Least Two DNA-binding Proteins and a Tripartite Architecture That Includes an Initiator Element

Luo

Gilinger

Mukherjee

et al. 1999

Journal of Biological Chemistry

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Eukaryotic transcriptional regulatory signals, defined as core and activator promoter elements, have yet to be identified in the earliest diverging group of eukaryotes, the primitive protozoans, which include the Trypanosomatidae family of parasites. The divergence within this family is highlighted by the apparent absence of the "universal" transcription factor TATA-binding protein. To understand gene expression in these protists, we have investigated spliced leader RNA gene transcription. The RNA product of this gene provides an m 7 G cap and a 39-nucleotide leader sequence to all cellular mRNAs via a trans-splicing reaction. Regulation of spliced leader RNA synthesis is controlled by a tripartite promoter located exclusively upstream from the transcription start site. Proteins PBP-1 and PBP-2 bind to two of the three promoter elements in the trypanosomatid Leptomonas seymouri. They represent the first trypanosome transcription factors with typical doublestranded DNA binding site recognition. These proteins ensure efficient transcription. However, accurate initiation is determined an initiator element with a a loose consensus of CYAC/AYR (؉1), which differs from that found in metazoan initiator elements as well as from that identified in one of the earliest diverging protozoans, Trichomonas vaginalis. Trypanosomes may utilize initiator element-protein interactions, and not TATA sequence-TATA-binding protein interactions, to direct proper transcription initiation by RNA polymerase II.Molecular studies of trypanosomatids, a ubiquitous and diverse family of protozoan pathogens, have revealed strikingly unusual mechanisms of mRNA synthesis. One central device is that two independent transcription events direct each mRNA produced in the trypanosome nucleus (for review, see Ref. 1). The protein-coding portion is transcribed as a single primary mRNA, often containing several open reading frames flanked by 5Ј-and 3Ј-untranslated regions. The capped 5Ј-end portion is transcribed as a short spliced leader (SL) 1 RNA. The two parts are fused in a trans-splicing reaction that yields a functional mRNA. During fusion, the 39 nt present on the 5Ј-end of the SL RNA (and referred to as the SL) are transferred to a region upstream from the coding region on the primary mRNA (2). Addition of the SL provides each mRNA with an m 7 G cap as well as four extensively methylated nucleotides, at positions 1-4 within the 39-nt SL RNA (3).The SL RNA is transcribed from a highly reiterated set of genes. In contrast to the long primary transcripts that form the bulk of the mature mRNA, each SL RNA has a discrete transcriptional start site. ␣-Amanitin studies show that it is very probable, though not proven, that the SL RNA gene is transcribed by RNA polymerase (pol) II. The primary SL RNA transcript and the transcript present in the trans-splicing spliceosome possess identical 5Ј-and 3Ј-ends, indicating that both transcription initiation and termination regulate the accumulation of SL RNA. SL RNA expression has been monitored using independe...

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An RNA Polymerase II Promoter in the hsp70 Locus of Trypanosoma brucei

Cited by 48 publications

References 50 publications

Cell Biology of the Trypanosome Genome

Cell Biology of the Trypanosome Genome

TcUBP-1, a Developmentally Regulated U-rich RNA-binding Protein Involved in Selective mRNA Destabilization in Trypanosomes

Transcription Initiation at the TATA-less Spliced Leader RNA Gene Promoter Requires at Least Two DNA-binding Proteins and a Tripartite Architecture That Includes an Initiator Element

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