28 research outputs found

    Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation control.

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    N6-methyladenosine (m6A) is an abundant internal RNA modification in both coding and non-coding RNAs that is catalysed by the METTL3-METTL14 methyltransferase complex. However, the specific role of these enzymes in cancer is still largely unknown. Here we define a pathway that is specific for METTL3 and is implicated in the maintenance of a leukaemic state. We identify METTL3 as an essential gene for growth of acute myeloid leukaemia cells in two distinct genetic screens. Downregulation of METTL3 results in cell cycle arrest, differentiation of leukaemic cells and failure to establish leukaemia in immunodeficient mice. We show that METTL3, independently of METTL14, associates with chromatin and localizes to the transcriptional start sites of active genes. The vast majority of these genes have the CAATT-box binding protein CEBPZ present at the transcriptional start site, and this is required for recruitment of METTL3 to chromatin. Promoter-bound METTL3 induces m6A modification within the coding region of the associated mRNA transcript, and enhances its translation by relieving ribosome stalling. We show that genes regulated by METTL3 in this way are necessary for acute myeloid leukaemia. Together, these data define METTL3 as a regulator of a chromatin-based pathway that is necessary for maintenance of the leukaemic state and identify this enzyme as a potential therapeutic target for acute myeloid leukaemia

    The structure of a micro-bat community in relation to gradients of environmental variation in a tropical urban area

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    We investigated patterns of community structure (species composition, foraging activity, and nightly foraging patterns) of bats in relation to gradients of environmental variation in a tropical urban area. A total of 32 sites spread equally across eight habitat types were sampled in the city of Townsville, North Queensland, Australia. Each site was sampled on 3 non-consecutive occasions using automated AnaBat systems. Eleven species were confidently identified while a possible four more were identified only to the genus level. Ordination of environmental variables measured at these sites identified two distinct environmental gradients reflecting the degree of urbanisation and foliage density. With in- creasing urbanisation there was a decline in species richness and total foraging activity. We used regression trees to characterise foraging preferences of each species. This analysis sug- gested that only one species of Mormopterus was able to exploit the resources provided by urbanisation. This species foraged in areas with higher numbers of white streetlights. The remaining species of bats preferred to forage within close proximity to natural vegetation and with low numbers of streetlights. The density of vegetation in long-established suburbs did not substantially reverse the trend for urban areas to have fewer bat species than original habitats

    Ants as indicators for vertebrate fauna at a local scale: an assessment of cross-taxa surrogacy in a disturbed matrix

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    We examined the spatial fidelity in the pattern in species richness, abundance and composition of ants, birds, mammals and reptiles in a Eucalyptus vegetation type in Australian tropical savanna woodland. We sampled 32 sites representing intact (uncleared) vegetation, and three treatments of different clearing age (2, 12 and 18 years). We investigated whether each fauna taxon could act a surrogate for pattern in the other, and whether they responded in parallel to time since clearing. Reptiles and mammals were combined into a single group. The correlation between taxa was low for abundance (the best being between rept/mamm and ant abundance R = 0.34) and moderate for species richness (varied from 0.36 to 0.44). Mantel tests identified a moderately strong relationship between bird and rept/mamm composition (R = 0.48). Recent clearing (2–12 years) depleted both abundance and species richness of the vertebrate fauna, whereas ant abun- dance spiked. Ant species richness was consistent over time since clearing. ANOSIM revealed that clearing age was a strong a priori predictor of birds and rept/mamm com- position (Global R = 0.48, 0.65, respectively), whereas it was not for ants (Global R = 0.20). Pair-wise comparisons suggested that for birds, rept/mamm, there was con- sistent changes in composition from intact woodlands to different aged clearing. This was not the case for ants; most distinct variation in composition occurred between treatments of increasing in clearing age (2–18 years R = 0.69, 12–18 years R = 0.65). The results of this study do not support the use of ants as a surrogate of vertebrates at a local scale in a cleared and intact vegetation mosaic. We acknowledge that identification of universal surrogates and indicators are difficult to find, but funding and political expediency that demand rapid solutions to conservation planning necessitate continued investigation of the merits of using surrogate species

    Prescribed fire in eucalypt woodlands: immediate effects on a microbat community of northern Australia

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    Context: Fire is a major ecological factor in many landscapes. Prescribed fires are often used in the management of vegetation for ecological values, wildlife habitat and reduction of risk of wildfire. However, debate continues over whether active fire management is beneficial to flora and fauna. Although bats comprise ~20% of the world’s extant mammal fauna, they have been largely ignored in studies investigating ecosystem response to fire, especially in Australia. Aims: In the present study, we aim to investigate the immediate responses of microbats to prescribed fires in a tropical eucalypt woodland. Methods: We used a replicated paired experimental design, consisting of burned and unburned treatment and control sites, to investigate how bat activity and community structure change following a prescribed fire. Key results: Total bat activity increased significantly following fire. Fire also resulted in changes in the bat species assemblage. Changes in community structure were driven by the following five species: Saccolaimus spp., Chalinolobus nigrogriseus, Chaerephon jobensis, Rhinolophus megaphyllus and unidentified Species c35. Activity of C. nigrogriseus, Saccolaimus spp., C. jobensis and Species c35 increased in the burned sites, whereas changes in the activity of R. megaphyllus were uncorrelated with the effects of fire.Conclusions: The effect of fire on these species is consistent with flight patterns and habitat use; species with higher wing aspect ratios, such as Saccolaimus spp., which are capable of fast flight but with limited manoeuvrability, became more active in the open conditions created by fire. Implications: The results of the present study suggest that prescribed fire as an environmental management tool may be beneficial to bats, at least in the short term, because it increases habitat suitability for a wider range of species.</p

    Bryophyte dispersal by flying foxes: A novel discovery

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    This research provides the first evidence of dispersal of bryophytes and associated microorganisms through ingestion by a highly mobile vertebrate vector, the spectacled flying fox (Pteropus conspicillatus). Bryophyte fragments were found in faeces collected at four P. conspicillatus' camps in the Wet Tropics bioregion, northeastern Australia. These fragments were viable when grown in culture; live invertebrates and other organisms were also present. Our study has significantly increased understanding of the role of flying foxes as dispersal vectors in tropical forests. © 2007 Springer-Verlag

    Dietary variation in spectacled flying foxes (Pteropus conspicillatus) of the Australian Wet Tropics

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    The diet of Pteropus conspicillatus, a large flying fox, was examined by collecting faeces in traps beneath daytime roost trees in four geographically distinct camps in the Wet Tropics bioregion of North-eastern Queensland, Australia. Faecal analyses revealed that P. conspicillatus utilise a broad variety of plant resources from a variety of habitats. Seed and pulp from figs (Ficus spp., Moraceae) and pollen from the family Myrtaceae were most frequently represented in the faeces from a range of both wet sclerophyll and rainforest habitats. The dietary composition of P. conspicillatus at individual camps could not be predicted by the habitats located within a typical foraging distance of each camp (20 km), and although consistent dietary changes were seen across all camps over time, each camp had a unique dietary signature indicative of feeding on a distinct subset of available vegetation. The unique diet of each camp and the variety of dietary items consumed suggest that camps may need to be managed on an individual camp-specific basis, and that P. conspicillatus are utilising a broader range of resources than would be expected if the species was a strict ‘rainforest-fruit specialist’.</i
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