About
44
Publications
5,440
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
804
Citations
Introduction
We have identified the human FMN2 gene as a novel target regulated by induction of p14ARF and by multiple stress responses, including DNA damage and hypoxia, which have activation of cell cycle arrest in common. Increased FMN2 protein levels promote cell cycle arrest by inhibiting the degradation of p21, and our data show that control of p21 stability is a key part of mechanisms that regulate p21 induction. We are also developing snoMEN™ protein replacement vector systems.
Current institution
Additional affiliations
October 2017 - October 2019
July 2007 - present
Position
- 1 ) Protein dynamics of tumour suppressing pathway 2 ) small nucleolar RNA modulated gene expression
April 2002 - March 2007
Education
April 2002 - March 2007
Publications
Publications (44)
African trypanosomes are highly divergent from their metazoan hosts, and as part of adaptation to a parasitic life style have developed a unique endomembrane system. The key virulence mechanism of many pathogens is successful immune evasion, to enable survival within a host, a feature that requires both genetic events and membrane transport mechani...
African trypanosomes are an early branch in eukaryotic evolution and developed a unique endomembrane system as an adaptation to their parasitic life style. The key virulence mechanism of many pathogens is successful immune evasion to enable survival within the host, which is a feature requiring both genetic events and membrane transport in African...
The snoMEN (snoRNA Modulator of gene ExpressioN) vector technology was developed from a human box C/D snoRNA, HBII-180C, which contains an internal sequence that can be manipulated to make it complementary to RNA targets, allowing knock-down of targeted genes. Here we have screened additional human nucleolar snoRNAs and assessed their application f...
Supporting Table of SILAC analysis.
(XLSX)
Supporting Table of in silico analysis.
(DOCX)
We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the sp...
We have identified the human FMN2 gene as a novel target regulated by induction of p14ARF and by multiple other stress responses, including DNA damage and hypoxia, which have in common activation of cell cycle arrest. We showed that increased expression of the FMN2 gene following p14ARF induction is caused, at the transcriptional level, by relief o...
The study of the function of many human proteins is often hampered by technical limitations, such as cytotoxicity and phenotypes that result from overexpression of the protein of interest together with the endogenous version. Here we present the snoMEN (snoRNA Modulator of gene ExpressioN) vector technology for generating stable cell lines where ex...
Gene-expression profile of snoMEN replacement stable cell lines. (A) Distribution pattern of GFP-SMN1 signal intensity of U2OSGFP–SMN1-PR stable cell line. Cytoplasmic GFP signals were calculated from randomly selected cells (n = 42). Each signal was normalised by DAPI signal. (B) Expression level comparison of proteins detected by Mass spectrometr...
Characterisation of FP–protein complexes in replacement stable cell lines by Quantitative SILAC Proteomic analysis. (A) SILAC result of GFP–SMN1 complex pull-down assay visualised on a 2D logarithmic graph. On the x axis, log2 (H/L ratio) correlates with the enrichment in GFP–SMN1 IP with protein replacement versus control IP. On the y axis, log2 (...
The list of SILAC ratio values of labelled proteins described in
Figure 2E
.
(XLSX)
The list of SILAC ratio values of top 10% labelled proteins described in Figure S5A.
(XLSX)
SiRNA and shRNA knock-down targeted to endogenous SMN1 pre-mRNAs. (A–D) These are the same experiment as in Figure 3C–F except the target gene is SMN1 in U2OS cells. (A) Scrambled siRNA (Negative control siRNA) and SMN1 siRNA (Dharmacon) were transfected as a negative and a positive control, respectively. SMN1 Mbox siRNA-1 to -3 (siSM1–3) have the...
SnoRNA expression analysis after Fibrillarin knock-down treatment. qRT-PCR was performed to measure snoRNA expression level after treatment with scramble siRNA (Control) and Fibrillarin siRNA. Equal amounts of total RNA from U2OSGFP–SMN1-PR cells, extracted following siRNA treatment, was used for qRT-PCR reactions. Graph shows the snoRNA expression...
Optimisation of RNA polymerase I inhibition using low concentration Actinomycin-D treatment. (A) In vivo transcription assay with/without Actinomycin-D treatment in HeLa cells. HeLa cells were treated either with ethanol (EtOH) as a negative control, or with Actinomycin-D (0.01 µg/ml) for each time point: 30 min, 1 hr, and 2 hr. Transcription in th...
The list of SILAC ratio values of top 10% labelled proteins described in
Figure 5B
.
(XLSX)
The list of SILAC ratio values of labelled proteins described in Figure S1B.
(XLSX)
The present invention relates to a method of targeting miRNA and/or pre-miRNA molecules in order to treat diseases that are linked with miRNA expression, such as certain cancers. The present invention also provides modified snoRNA molecules for targeting mi RNA molecules for use in treating diseases that are linked with miRNA expression, such as ce...
The ARF tumor suppressor is a central component of the cellular defense against oncogene activation in mammals. p14ARF activates p53 by binding and inhibiting HDM2, resulting, inter alia, in increased transcription and expression of the cyclin-dependent kinase inhibitor p21 and consequent cell-cycle arrest. We analyzed the effect of p14ARF inductio...
Small nucleolar RNAs (snoRNAs) function mainly as guides for the post-transcriptional modification of ribosomal RNAs (rRNAs).
In recent years, several studies have identified a wealth of small fragments (<35 nt) derived from snoRNAs (termed sdRNAs)
that stably accumulate in the cell, some of which may regulate splicing or translation. A comparison...
The present invention provides methods for diagnosing cell proliferation and/or differentiation disorders, compounds and methods for treating the same and methods for identifying agents potentially useful in the treatment of cell proliferation and/or differentiation disorders.
There are two main classes of small nucleolar RNAs (snoRNAs): the box C/D snoRNAs and the box H/ACA snoRNAs that function
as guide RNAs to direct sequence-specific modification of rRNA precursors and other nucleolar RNA targets. A previous computational
and biochemical analysis revealed a possible evolutionary relationship between miRNA precursors...
Yeast cells lacking Ctf18, the major subunit of an alternative Replication Factor C complex, have multiple problems with genome stability. To understand the in vivo function of the Ctf18 complex, we analyzed chromatin composition in a ctf18Δ mutant using the quantitative proteomic technique of stable isotope labeling by amino acids in cell culture....
Monitoring Editor: A. Gregory Matera Human snoRNAs that copurify with nucleoli isolated from HeLa cells have been characterized. Novel fibrillarin-associated snoRNAs were detected that allowed the creation of a new vector system for the targeted knock-down of one or more genes in mammalian cells. The snoMEN (snoRNA Modulator of gene ExpressioN) vec...
Human small nucleolar RNAs (snoRNAs) that copurify with nucleoli isolated from HeLa cells have been characterized. Novel fibrillarin-associated snoRNAs were detected that allowed the creation of a new vector system for the targeted knockdown of one or more genes in mammalian cells. The snoMEN (snoRNA modulator of gene expressioN) vector technology...
Extracellular signal-regulated kinase (ERK) controls fundamental cellular functions, including cell fate decisions. In PC12, cells shifting ERK activation from transient to sustained induces neuronal differentiation. As ERK associates with both regulators and effectors, we hypothesized that the mechanisms underlying the switch could be revealed by...
Sox15 belongs to the Sox (Sry-type HMG box) protein family, which is involved in placental development and muscle regeneration. Previously, we showed that the Sox15 gene is highly expressed in the trophoblast giant cells of the mouse placenta. To elucidate the molecular mechanisms of the tissue-dependent transcription of the gene, we isolated appro...
Some members of the Sry-type HMG box (Sox) protein family play important roles in embryogenesis as transcription factors. Here, we report that Sox15 transcripts were much more abundant in mouse placenta than in the fetus, the yolk sac, or several adult tissues. In situ hybridization analysis of the mouse E8.0 conceptus indicated that Sox15 mRNA was...
In rainbow trout, there are at least two CYP19 genes (CYP19a and CYP19b). They encode distinct P450arom isozymes that are differentially expressed in the ovary and brain. To understand the transcriptional regulation of the rainbow trout CYP19a (rtCYP19a) gene in the ovary, we isolated its 5'-flanking region. The presence of potential FTZ-F1-binding...
