Publications by authors named "Michael Tellier"

19 Publications

  • Page 1 of 1

The 7SK/P-TEFb snRNP controls ultraviolet radiation-induced transcriptional reprogramming.

Cell Rep 2021 Apr;35(2):108965

Molecular, Cellular and Developmental Biology Department (MCD), Centre de Biologie Intégrative (CBI), University of Toulouse, CNRS, UPS, 31062 Toulouse, France. Electronic address:

Conversion of promoter-proximally paused RNA polymerase II (RNAPII) into elongating polymerase by the positive transcription elongation factor b (P-TEFb) is a central regulatory step of mRNA synthesis. The activity of P-TEFb is controlled mainly by the 7SK small nuclear ribonucleoprotein (snRNP), which sequesters active P-TEFb into inactive 7SK/P-TEFb snRNP. Here we demonstrate that under normal culture conditions, the lack of 7SK snRNP has only minor impacts on global RNAPII transcription without detectable consequences on cell proliferation. However, upon ultraviolet (UV)-light-induced DNA damage, cells lacking 7SK have a defective transcriptional response and reduced viability. Both UV-induced release of "lesion-scanning" polymerases and activation of key early-responsive genes are compromised in the absence of 7SK. Proper induction of 7SK-dependent UV-responsive genes requires P-TEFb activity directly mobilized from the nucleoplasmic 7SK/P-TEFb snRNP. Our data demonstrate that the primary function of the 7SK/P-TEFb snRNP is to orchestrate the proper transcriptional response to stress.
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http://dx.doi.org/10.1016/j.celrep.2021.108965DOI Listing
April 2021

CDK12 globally stimulates RNA polymerase II transcription elongation and carboxyl-terminal domain phosphorylation.

Nucleic Acids Res 2020 08;48(14):7712-7727

Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.

Cyclin-dependent kinase 12 (CDK12) phosphorylates the carboxyl-terminal domain (CTD) of RNA polymerase II (pol II) but its roles in transcription beyond the expression of DNA damage response genes remain unclear. Here, we have used TT-seq and mNET-seq to monitor the direct effects of rapid CDK12 inhibition on transcription activity and CTD phosphorylation in human cells. CDK12 inhibition causes a genome-wide defect in transcription elongation and a global reduction of CTD Ser2 and Ser5 phosphorylation. The elongation defect is explained by the loss of the elongation factors LEO1 and CDC73, part of PAF1 complex, and SPT6 from the newly-elongating pol II. Our results indicate that CDK12 is a general activator of pol II transcription elongation and indicate that it targets both Ser2 and Ser5 residues of the pol II CTD.
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http://dx.doi.org/10.1093/nar/gkaa514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641311PMC
August 2020

Incomplete removal of ribosomal RNA can affect chromatin RNA-seq data analysis.

Transcription 2020 10 30;11(5):230-235. Epub 2020 Jul 30.

Sir William Dunn School of Pathology, University of Oxford , Oxford, UK.

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http://dx.doi.org/10.1080/21541264.2020.1794491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714438PMC
October 2020

CRISPRing for host genes regulating SARS-CoV-2.

Nat Rev Immunol 2020 09;20(9):518

OxImmuno Literature Initiative, University of Oxford, Oxford, UK.

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http://dx.doi.org/10.1038/s41577-020-0400-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351543PMC
September 2020

Transcription and splicing: A two-way street.

Wiley Interdiscip Rev RNA 2020 09 3;11(5):e1593. Epub 2020 Mar 3.

Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.

RNA synthesis by RNA polymerase II and RNA processing are closely coupled during the transcription cycle of protein-coding genes. This coupling affords opportunities for quality control and regulation of gene expression and the effects can go in both directions. For example, polymerase speed can affect splice site selection and splicing can increase transcription and affect the chromatin landscape. Here we review the many ways that transcription and splicing influence one another, including how splicing "talks back" to transcription. We will also place the connections between transcription and splicing in the context of other RNA processing events that define the exons that will make up the final mRNA. This article is categorized under: RNA Processing > Splicing Mechanisms RNA Processing > Splicing Regulation/Alternative Splicing.
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http://dx.doi.org/10.1002/wrna.1593DOI Listing
September 2020

Compensating for over-production inhibition of the Hsmar1 transposon in using a series of constitutive promoters.

Mob DNA 2020 10;11. Epub 2020 Jan 10.

School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH UK.

Background: Transposable elements (TEs) are a diverse group of self-mobilizing DNA elements. Transposition has been exploited as a powerful tool for molecular biology and genomics. However, transposition is sometimes limited because of auto-regulatory mechanisms that presumably allow them to cohabit within their hosts without causing excessive genomic damage. The papillation assay provides a powerful visual screen for hyperactive transposases. Transposition is revealed by the activation of a promoter-less gene when the transposon integrates into a non-essential gene on the host chromosome. Transposition events are detected as small blue speckles, or papillae, on the white background of the main colony.

Results: We analysed the parameters of the papillation assay including the strength of the transposase transcriptional and translational signals. To overcome certain limitations of inducible promoters, we constructed a set of vectors based on constitutive promoters of different strengths to widen the range of transposase expression. We characterized and validated our expression vectors with Hsmar1, a member of the transposon family. The highest rate of transposition was observed with the weakest promoters. We then took advantage of our approach to investigate how the level of transposition responds to selected point mutations and the effect of joining the transposase monomers into a single-chain dimer.

Conclusions: We generated a set of vectors to provide a wide range of transposase expression which will be useful for screening libraries of transposase mutants. The use of weak promoters should allow screening for truly hyperactive transposases rather than those that are simply resistant to auto-regulatory mechanisms, such as overproduction inhibition (OPI). We also found that mutations in the Hsmar1 dimer interface provide resistance to OPI in bacteria, which could be valuable for improving bacterial transposon mutagenesis techniques.
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http://dx.doi.org/10.1186/s13100-020-0200-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954556PMC
January 2020

Effect of CFIm68 knockdown on RNA polymerase II transcription.

BMC Res Notes 2019 Sep 2;12(1):554. Epub 2019 Sep 2.

Sir William Dunn School of Pathology, University of Oxford, South Park Roads, Oxford, OX1 3RE, UK.

Objectives: Transcription of eukaryotic protein-coding genes by RNA polymerase II (pol II) is highly regulated at initiation, elongation and termination. Transcription is also coordinated with co-transcriptional processing of the emerging pre-mRNA by capping, splicing, and cleavage and polyadenylation. Polyadenylation (poly(A)) site recognition, which defines the end of the mRNA, relies on the cleavage and polyadenylation (CPA) complex. It was previously observed that knocking-down proteins of the CPA complex affects not only recognition of the poly(A) site but also results in increased pausing of pol II at the beginning of genes. This finding suggests that the CPA complex plays a role in regulating pol II turnover after transcription initiation.

Data Description: To explore this possibility, we knocked-down a subunit of the cleavage factor I (CFIm), CFIm68, which is part of the CPA complex and involved in alternative polyadenylation, and performed pol II ChIP-seq in absence or presence of a transcription elongation inhibitor. In addition, we performed pol II ChIP-qPCR on a subset of protein coding genes after knocking down CFIm68.
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http://dx.doi.org/10.1186/s13104-019-4582-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720987PMC
September 2019

The roles of the human SETMAR (Metnase) protein in illegitimate DNA recombination and non-homologous end joining repair.

DNA Repair (Amst) 2019 08 19;80:26-35. Epub 2019 Jun 19.

School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK. Electronic address:

SETMAR is a fusion between a SET-domain methyltransferase gene and a mariner-family transposase gene, which is specific to anthropoid primates. However, the ancestral SET gene is present in all other mammals and birds. SETMAR is reported to be involved in transcriptional regulation and a diverse set of reactions related to DNA repair. Since the transcriptional effects of SETMAR depend on site-specific DNA binding, and are perturbed by inactivating the methyltransferase, we wondered whether we could differentiate the effects of the SET and MAR domains in DNA repair assays. We therefore generated several stable U2OS cell lines expressing either wild type SETMAR or truncation or point mutant variants. We tested these cell lines with in vivo plasmid-based assays to determine the relevance of the different domains and activities of SETMAR in DNA repair. Contrary to previous reports, we found that wild type SETMAR had little to no effect on the rate of cell division, DNA integration into the genome or non-homologous end joining. Also contrary to previous reports, we failed to detect any effect of a strong active-site mutation that should have knocked out the putative nuclease activity of SETMAR.
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http://dx.doi.org/10.1016/j.dnarep.2019.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715855PMC
August 2019

Effect of CFIm25 knockout on RNA polymerase II transcription.

BMC Res Notes 2018 Dec 14;11(1):894. Epub 2018 Dec 14.

Sir William Dunn School of Pathology, University of Oxford, South Park Roads, Oxford, OX1 3RE, UK.

Objectives: Transcription of eukaryotic protein-coding genes by RNA polymerase II (pol II) is a highly regulated process. Most human genes have multiple poly(A) sites, which define different possible mRNA ends, suggesting the existence of mechanisms that regulate which poly(A) site is used. Poly(A) site selection may be mediated by cleavage factor I (CFIm), which is part of the cleavage and polyadenylation (CPA) complex. CFIm comprises CFIm25, CFIm59 and CFim68 subunits. It has been documented that the CPA complex also regulates pol II transcription at the start of genes. We therefore investigated whether CFIm, in addition to its role in poly(A) site selection, is involved in the regulation of pol II transcription.

Data Description: We provide genome-wide data of the effect of reducing by 90% expression of the CFIm25 constituent of CFIm, which is involved in pre-mRNA cleavage and polyadenylation, on pol II transcription in human cells. We performed pol II ChIP-seq in the presence or absence of CFIm25 and with or without an inhibitor of the cyclin-dependent kinase (CDK)9, which regulates the entry of pol II into productive elongation.
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http://dx.doi.org/10.1186/s13104-018-4006-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295108PMC
December 2018

Deregulated Expression of Mammalian lncRNA through Loss of SPT6 Induces R-Loop Formation, Replication Stress, and Cellular Senescence.

Mol Cell 2018 12 15;72(6):970-984.e7. Epub 2018 Nov 15.

Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. Electronic address:

Extensive tracts of the mammalian genome that lack protein-coding function are still transcribed into long noncoding RNA. While these lncRNAs are generally short lived, length restricted, and non-polyadenylated, how their expression is distinguished from protein-coding genes remains enigmatic. Surprisingly, depletion of the ubiquitous Pol-II-associated transcription elongation factor SPT6 promotes a redistribution of H3K36me3 histone marks from active protein coding to lncRNA genes, which correlates with increased lncRNA transcription. SPT6 knockdown also impairs the recruitment of the Integrator complex to chromatin, which results in a transcriptional termination defect for lncRNA genes. This leads to the formation of extended, polyadenylated lncRNAs that are both chromatin restricted and form increased levels of RNA:DNA hybrid (R-loops) that are associated with DNA damage. Additionally, these deregulated lncRNAs overlap with DNA replication origins leading to localized DNA replication stress and a cellular senescence phenotype. Overall, our results underline the importance of restricting lncRNA expression.
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http://dx.doi.org/10.1016/j.molcel.2018.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309921PMC
December 2018

Human SETMAR is a DNA sequence-specific histone-methylase with a broad effect on the transcriptome.

Nucleic Acids Res 2019 01;47(1):122-133

School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.

Transposons impart dynamism to the genomes they inhabit and their movements frequently rewire the control of nearby genes. Occasionally, their proteins are domesticated when they evolve a new function. SETMAR is a protein methylase with a sequence-specific DNA binding domain. It began to evolve about 50 million years ago when an Hsmar1 transposon integrated downstream of a SET-domain methylase gene. Here we show that the DNA-binding domain of the transposase targets the enzyme to transposon-end remnants and that this is capable of regulating gene expression, dependent on the methylase activity. When SETMAR was modestly overexpressed in human cells, almost 1500 genes changed expression by more than 2-fold (65% up- and 35% down-regulated). These genes were enriched for the KEGG Pathways in Cancer and include several transcription factors important for development and differentiation. Expression of a similar level of a methylase-deficient SETMAR changed the expression of many fewer genes, 77% of which were down-regulated with no significant enrichment of KEGG Pathways. Our data is consistent with a model in which SETMAR is part of an anthropoid primate-specific regulatory network centered on the subset of genes containing a transposon end.
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http://dx.doi.org/10.1093/nar/gky937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326780PMC
January 2019

Transposase subunit architecture and its relationship to genome size and the rate of transposition in prokaryotes and eukaryotes.

Nucleic Acids Res 2018 10;46(18):9637-9646

School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.

Cut-and-paste transposons are important tools for mutagenesis, gene-delivery and DNA sequencing applications. At the molecular level, the most thoroughly understood are Tn5 and Tn10 in bacteria, and mariner and hAT elements in eukaryotes. All bacterial cut-and-paste transposases characterized to date are monomeric prior to interacting with the transposon end, while all eukaryotic transposases are multimers. Although there is a limited sample size, we proposed that this defines two pathways for transpososome assembly which distinguishes the mechanism of the bacterial and eukaryotic transposons. We predicted that the respective pathways would dictate how the rate of transposition is related to transposase concentration and genome size. Here, we have tested these predictions by creating a single-chain dimer version of the bacterial Tn5 transposase. We show that artificial dimerization switches the transpososome assembly pathway from the bacterial-style to the eukaryotic-style. Although this had no effect in vitro, where the transposase does not have to search far to locate the transposon ends, it increased the rate of transposition in bacterial and HeLa cell assays. However, in contrast to the mariner elements, the Tn5 single-chain dimer remained unaffected by over-production inhibition, which is an emergent property of the transposase subunit structure in the mariner elements.
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http://dx.doi.org/10.1093/nar/gky794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182136PMC
October 2018

Influenza Virus Mounts a Two-Pronged Attack on Host RNA Polymerase II Transcription.

Cell Rep 2018 05;23(7):2119-2129.e3

Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. Electronic address:

Influenza virus intimately associates with host RNA polymerase II (Pol II) and mRNA processing machinery. Here, we use mammalian native elongating transcript sequencing (mNET-seq) to examine Pol II behavior during viral infection. We show that influenza virus executes a two-pronged attack on host transcription. First, viral infection causes decreased Pol II gene occupancy downstream of transcription start sites. Second, virus-induced cellular stress leads to a catastrophic failure of Pol II termination at poly(A) sites, with transcription often continuing for tens of kilobases. Defective Pol II termination occurs independently of the ability of the viral NS1 protein to interfere with host mRNA processing. Instead, this termination defect is a common effect of diverse cellular stresses and underlies the production of previously reported downstream-of-gene transcripts (DoGs). Our work has implications for understanding not only host-virus interactions but also fundamental aspects of mammalian transcription.
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http://dx.doi.org/10.1016/j.celrep.2018.04.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972227PMC
May 2018

DOT1L and H3K79 Methylation in Transcription and Genomic Stability.

Biomolecules 2018 02 27;8(1). Epub 2018 Feb 27.

Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.

The organization of eukaryotic genomes into chromatin provides challenges for the cell to accomplish basic cellular functions, such as transcription, DNA replication and repair of DNA damage. Accordingly, a range of proteins modify and/or read chromatin states to regulate access to chromosomal DNA. Yeast Dot1 and the mammalian homologue DOT1L are methyltransferases that can add up to three methyl groups to histone H3 lysine 79 (H3K79). H3K79 methylation is implicated in several processes, including transcription elongation by RNA polymerase II, the DNA damage response and cell cycle checkpoint activation. DOT1L is also an important drug target for treatment of mixed lineage leukemia (MLL)-rearranged leukemia where aberrant transcriptional activation is promoted by DOT1L mislocalisation. This review summarizes what is currently known about the role of Dot1/DOT1L and H3K79 methylation in transcription and genomic stability.
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http://dx.doi.org/10.3390/biom8010011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871980PMC
February 2018

The 7SK snRNP associates with the little elongation complex to promote snRNA gene expression.

EMBO J 2017 04 2;36(7):934-948. Epub 2017 Mar 2.

Laboratoire de Biologie Moléculaire Eucaryote, Centre de Biologie Intégrative (CBI), CNRS, UPS, Université de Toulouse, Toulouse Cedex 9, France

The 7SK small nuclear RNP (snRNP), composed of the 7SK small nuclear RNA (snRNA), MePCE, and Larp7, regulates the mRNA elongation capacity of RNA polymerase II (RNAPII) through controlling the nuclear activity of positive transcription elongation factor b (P-TEFb). Here, we demonstrate that the human 7SK snRNP also functions as a canonical transcription factor that, in collaboration with the little elongation complex (LEC) comprising ELL, Ice1, Ice2, and ZC3H8, promotes transcription of RNAPII-specific spliceosomal snRNA and small nucleolar RNA (snoRNA) genes. The 7SK snRNA specifically associates with a fraction of RNAPII hyperphosphorylated at Ser5 and Ser7, which is a hallmark of RNAPII engaged in snRNA synthesis. Chromatin immunoprecipitation (ChIP) and chromatin isolation by RNA purification (ChIRP) experiments revealed enrichments for all components of the 7SK snRNP on RNAPII-specific sn/snoRNA genes. Depletion of 7SK snRNA or Larp7 disrupts LEC integrity, inhibits RNAPII recruitment to RNAPII-specific sn/snoRNA genes, and reduces nascent snRNA and snoRNA synthesis. Thus, through controlling both mRNA elongation and sn/snoRNA synthesis, the 7SK snRNP is a key regulator of nuclear RNA production by RNAPII.
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http://dx.doi.org/10.15252/embj.201695740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376971PMC
April 2017

The point of no return: The poly(A)-associated elongation checkpoint.

RNA Biol 2016 6;13(3):265-71. Epub 2016 Feb 6.

a Sir William Dunn School of Pathology, University of Oxford , Oxford OX1 3RE , UK.

Cyclin-dependent kinases play critical roles in transcription by RNA polymerase II (pol II) and processing of the transcripts. For example, CDK9 regulates transcription of protein-coding genes, splicing, and 3' end formation of the transcripts. Accordingly, CDK9 inhibitors have a drastic effect on the production of mRNA in human cells. Recent analyses indicate that CDK9 regulates transcription at the early-elongation checkpoint of the vast majority of pol II-transcribed genes. Our recent discovery of an additional CDK9-regulated elongation checkpoint close to poly(A) sites adds a new layer to the control of transcription by this critical cellular kinase. This novel poly(A)-associated checkpoint has the potential to powerfully regulate gene expression just before a functional polyadenylated mRNA is produced: the point of no return. However, many questions remain to be answered before the role of this checkpoint becomes clear. Here we speculate on the possible biological significance of this novel mechanism of gene regulation and the players that may be involved.
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http://dx.doi.org/10.1080/15476286.2016.1142037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829286PMC
December 2016

CTCF regulates NELF, DSIF and P-TEFb recruitment during transcription.

Transcription 2015 23;6(5):79-90. Epub 2015 Sep 23.

a Sir William Dunn School of Pathology; University of Oxford ; Oxford , UK.

CTCF is a versatile transcription factor with well-established roles in chromatin organization and insulator function. Recent findings also implicate CTCF in the control of elongation by RNA polymerase (RNAP) II. Here we show that CTCF knockdown abrogates RNAP II pausing at the early elongation checkpoint of c-myc by affecting recruitment of DRB-sensitivity-inducing factor (DSIF). CTCF knockdown also causes a termination defect on the U2 snRNA genes (U2), by affecting recruitment of negative elongation factor (NELF). In addition, CTCF is required for recruitment of positive elongation factor b (P-TEFb), which phosphorylates NELF, DSIF, and Ser2 of the RNAP II CTD to activate elongation of transcription of c-myc and recognition of the snRNA gene-specific 3' box RNA processing signal. These findings implicate CTCF in a complex network of protein:protein/protein:DNA interactions and assign a key role to CTCF in controlling RNAP II transcription through the elongation checkpoint of the protein-coding c-myc and the termination site of the non-coding U2, by regulating the recruitment and/or activity of key players in these processes.
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http://dx.doi.org/10.1080/21541264.2015.1095269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802788PMC
October 2016

Mariner and the ITm Superfamily of Transposons.

Microbiol Spectr 2015 Apr;3(2):MDNA3-0033-2014.

School of Life Sciences, University of Nottingham, QMC, Nottingham, NG7 2UH, UK.

The IS630-Tc1-mariner (ITm) family of transposons is one of the most widespread in nature. The phylogenetic distribution of its members shows that they do not persist for long in a given lineage, but rely on frequent horizontal transfer to new hosts. Although they are primarily selfish genomic-parasites, ITm transposons contribute to the evolution of their hosts because they generate variation and contribute protein domains and regulatory regions. Here we review the molecular mechanism of ITm transposition and its regulation. We focus mostly on the mariner elements, which are understood in the greatest detail owing to in vitro reconstitution and structural analysis. Nevertheless, the most important characteristics are probably shared across the grouping. Members of the ITm family are mobilized by a cut-and-paste mechanism and integrate at 5'-TA dinucleotide target sites. The elements encode a single transposase protein with an N-terminal DNA-binding domain and a C-terminal catalytic domain. The phosphoryl-transferase reactions during the DNA-strand breaking and joining reactions are performed by the two metal-ion mechanism. The metal ions are coordinated by three or four acidic amino acid residues located within an RNase H-like structural fold. Although all of the strand breaking and joining events at a given transposon end are performed by a single molecule of transposase, the reaction is coordinated by close communication between transpososome components. During transpososome assembly, transposase dimers compete for free transposon ends. This helps to protect the host by dampening an otherwise exponential increase in the rate of transposition as the copy number increases.
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http://dx.doi.org/10.1128/microbiolspec.MDNA3-0033-2014DOI Listing
April 2015

One to rule them all: A highly conserved motif in mariner transposase controls multiple steps of transposition.

Mob Genet Elements 2014 Jan 14;4(1):e28807. Epub 2014 Apr 14.

School of Life Sciences; University of Nottingham; Queen's Medical Centre; Nottingham, UK.

The development of transposon-based genome manipulation tools can benefit greatly from understanding transposons' inherent regulatory mechanisms. The Tc1-mariner transposons, which are being widely used in biotechnological applications, are subject to a self-inhibitory mechanism whereby increasing transposase expression beyond a certain point decreases the rate of transposition. In a recent paper, Liu and Chalmers performed saturating mutagenesis on the highly conserved WVPHEL motif in the mariner-family transposase from the Hsmar1 element. Curiously, they found that the majority of all possible single mutations were hyperactive. Biochemical characterizations of the mutants revealed that the hyperactivity is due to a defect in communication between transposase subunits, which normally regulates transposition by reducing the rate of synapsis. This provides important clues for improving transposon-based tools. However, some WVPHEL mutants also showed features that would be undesirable for most biotechnological applications: they showed uncontrolled DNA cleavage activities and defects in the coordination of cleavage between the two transposon ends. The study illustrates how the knowledge of inhibitory mechanisms can help improve transposon tools but also highlights an important challenge, which is to specifically target a regulatory mechanism without affecting other important functions of the transposase.
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http://dx.doi.org/10.4161/mge.28807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013102PMC
January 2014