Argonaute2 Is the Catalytic Engine of Mammalian RNAi Liu, Jidong; Carmell, Michelle A.; Rivas, Fabiola V. ...
Science (American Association for the Advancement of Science),
09/2004, Letnik:
305, Številka:
5689
Journal Article
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Gene silencing through RNA interference (RNAi) is carried out by RISC, the RNA-induced silencing complex. RISC contains two signature components, small interfering RNAs (siRNAs) and Argonaute family ...proteins. Here, we show that the multiple Argonaute proteins present in mammals are both biologically and biochemically distinct, with a single mammalian family member, Argonaute2, being responsible for messenger RNA cleavage activity. This protein is essential for mouse development, and cells lacking Argonaute2 are unable to mount an experimental response to siRNAs. Mutations within a cryptic ribonuclease H domain within Argonaute2, as identified by comparison with the structure of an archeal Argonaute protein, inactivate RISC. Thus, our evidence supports a model in which Argonaute contributes "Slicer" activity to RISC, providing the catalytic engine for RNAi.
The aim of this study was to investigate the hypothesis that changes in circulating microRNAs (miRs) represent potentially useful biomarkers for the diagnosis, staging and prediction of outcome in ...prostate cancer.
Real-time polymerase chain reaction analysis of 742 miRs was performed using plasma-derived circulating microvesicles of 78 prostate cancer patients and 28 normal control individuals to identify differentially quantified miRs.
A total of 12 miRs were differentially quantified in prostate cancer patients compared with controls, including 9 in patients without metastases. In all, 11 miRs were present in significantly greater amounts in prostate cancer patients with metastases compared with those without metastases. The association of miR-141 and miR-375 with metastatic prostate cancer was confirmed using serum-derived exosomes and microvesicles in a separate cohort of patients with recurrent or non-recurrent disease following radical prostatectomy. An analysis of five selected miRs in urine samples found that miR-107 and miR-574-3p were quantified at significantly higher concentrations in the urine of men with prostate cancer compared with controls.
These observations suggest that changes in miR concentration in prostate cancer patients may be identified by analysing various body fluids. Moreover, circulating miRs may be used to diagnose and stage prostate cancer.
The potential for Planck to detect clusters of dusty, star-forming galaxies at z > 1 is tested by examining the Herschel-SPIRE images of Planck Early Release Compact Source Catalog sources lying in ...fields observed by the Herschel Multitiered Extragalactic Survey. Of the 16 Planck sources that lie in the ∼90 sq. deg. examined, we find that 12 are associated with single bright Herschel sources. The remaining four are associated with overdensities of Herschel sources, making them candidate clusters of dusty, star-forming galaxies. We use complementary optical/near-IR data for these 'clumps' to test this idea, and find evidence for the presence of galaxy clusters in all four cases. We use photometric redshifts and red sequence galaxies to estimate the redshifts of these clusters, finding that they range from 0.8 to 2.3. These redshifts imply that the Herschel sources in these clusters, which contribute to the detected Planck flux, are forming stars very rapidly, with typical total cluster star formation rates >1000 M yr−1. The high-redshift clusters discovered in these observations are used to constrain the epoch of cluster galaxy formation, finding that the galaxies in our clusters are 1-1.5 Gyr old at z ∼ 1-2. Prospects for the discovery of further clusters of dusty galaxies are discussed, using not only all sky Planck surveys, but also deeper, smaller area, Herschel surveys.
We present a catalogue of ~3000 submillimetre sources detected ( greater than or equal to 3.5...) at 850 ...m over ~5 deg super( 2) surveyed as part of the James Clerk Maxwell Telescope (JCMT) ...SCUBA-2 Cosmology Legacy Survey (S2CLS). This is the largest survey of its kind at 850 ...m, increasing the sample size of 850 ...m selected submillimetre galaxies by an order of magnitude. The wide 850 ...m survey component of S2CLS covers the extragalactic fields: UKIDSS-UDS, COSMOS, Akari-NEP, Extended Groth Strip, Lockman Hole North, SSA22 and GOODS-North. The average 1... depth of S2CLS is 1.2 mJy beam super( -1), approaching the SCUBA-2 850 ...m confusion limit, which we determine to be ... 0.8 mJy beam super( -1). We measure the 850 ...m number counts, reducing the Poisson errors on the differential counts to approximately 4 per cent at S sub( 850) ... 3 mJy. With several independent fields, we investigate field-to-field variance, finding that the number counts on 0.5...-1... scales are generally within 50 per cent of the S2CLS mean for S sub( 850) > 3 mJy, with scatter consistent with the Poisson and estimated cosmic variance uncertainties, although there is a marginal (2...) density enhancement in GOODS-North. The observed counts are in reasonable agreement with recent phenomenological and semi-analytic models, although determining the shape of the faint-end slope (S sub( 850) < 3 mJy) remains a key test. The large solid angle of S2CLS allows us to measure the bright-end counts: at S sub( 850) > 10 mJy there are approximately 10 sources per square degree, and we detect the distinctive up-turn in the number counts indicative of the detection of local sources of 850 ...m emission, and strongly lensed high-redshift galaxies. All calibrated maps and the catalogue are made publicly available. (ProQuest: ... denotes formulae/symbols omitted.)
Stellar archaeology shows that massive elliptical galaxies formed rapidly about ten billion years ago with star-formation rates of above several hundred solar masses per year. Their progenitors are ...probably the submillimetre bright galaxies at redshifts z greater than 2. Although the mean molecular gas mass (5 × 10(10) solar masses) of the submillimetre bright galaxies can explain the formation of typical elliptical galaxies, it is inadequate to form elliptical galaxies that already have stellar masses above 2 × 10(11) solar masses at z ≈ 2. Here we report multi-wavelength high-resolution observations of a rare merger of two massive submillimetre bright galaxies at z = 2.3. The system is seen to be forming stars at a rate of 2,000 solar masses per year. The star-formation efficiency is an order of magnitude greater than that of normal galaxies, so the gas reservoir will be exhausted and star formation will be quenched in only around 200 million years. At a projected separation of 19 kiloparsecs, the two massive starbursts are about to merge and form a passive elliptical galaxy with a stellar mass of about 4 × 10(11) solar masses. We conclude that gas-rich major galaxy mergers with intense star formation can form the most massive elliptical galaxies by z ≈ 1.5.
We have constructed an extended halo model (EHM) which relates the total stellar mass and star-formation rate (SFR) to halo mass (M
h). An empirical relation between the distribution functions of ...total stellar mass of galaxies and host halo mass, tuned to match the spatial density of galaxies over 0 < z < 2 and the clustering properties at z ∼ 0, is extended to include two different scenarios describing the variation of SFR on M
h. We also present new measurements of the redshift evolution of the average SFR for star-forming galaxies of different stellar masses up to z = 2, using data from the Herschel Multi-tiered Extragalactic Survey for infrared bright galaxies.
Combining the EHM with the halo accretion histories from numerical simulations, we trace the stellar mass growth and star-formation history in haloes spanning a range of masses. We find that: (1) the intensity of the star-forming activity in haloes in the probed mass range has steadily decreased from z ∼ 2 to 0; (2) at a given epoch, haloes in the mass range between a few times 1011 M and a few times 1012 M are the most efficient at hosting star formation; (3) the peak of SFR density shifts to lower mass haloes over time; and (4) galaxies that are forming stars most actively at z ∼ 2 evolve into quiescent galaxies in today's group environments, strongly supporting previous claims that the most powerful starbursts at z ∼ 2 are progenitors of today's elliptical galaxies.
The RAD51 protein plays a key role in the homology-directed repair of DNA double-strand breaks and is important for maintaining genome stability. Here we report on a novel human RAD51 variant found ...in an aggressive and therapy-refractive breast carcinoma. Expression of the RAD51 G151D variant in human breast epithelial cells increases the levels of homology-directed repair. Expression of RAD51 G151D in cells also promotes high levels of chromosomal aberrations and sister chromatid exchanges. In vitro, the purified RAD51 G151D protein directly and significantly enhances DNA strand exchange activity in the presence of RPA. In concordance with this result, co-incubation of G151D with BRCA2 resulted in a much higher level of strand-exchange activity compared to WT RAD51. Strikingly, the RAD51 G151D variant confers resistance to multiple DNA damaging agents, including ionizing radiation, mitomycin C, and doxorubicin. Our findings demonstrate that the RAD51 G151D somatic variant has a novel hyper-recombination phenotype and suggest that this property of the protein is important for the repair of DNA damage, leading to drug resistance.
We present measurements of the auto- and cross-frequency power spectra of the cosmic infrared background (CIB) at 250, 350, and 500 mu m (1200, 860, and 600 GHz) from observations totaling ~70 deg ...sub(2) made with the SPIRE instrument aboard the Herschel Space Observatory. We measure a fractional anisotropy delta I/I = 14% + or - 4% , detecting signatures arising from the clustering of dusty star-forming galaxies in both the linear (2-halo) and nonlinear (1-halo) regimes; and that the transition from the 2- to 1-halo terms, below which power originates predominantly from multiple galaxies within dark matter halos, occurs at k sub(theta) ~ 0.10-0.12 aremin super(-1) (l ~ 2160-2380), from 250 to 500 mu m. We measure the cross-correlation power spectra between bands, finding that bands which are farthest apart are the least correlated, as well as hints of a reduction in the correlation between bands when resolved sources are more aggressively masked.
The Balloon-borne Large Aperture Submillimeter Telescope (BLAST) is a suborbital surveying experiment designed to study the evolutionary history and processes of star formation in local galaxies ...(including the Milky Way) and galaxies at cosmological distances. The BLAST continuum camera, which consists of 270 detectors distributed between three arrays, observes simultaneously in broadband (30%) spectral windows at 250, 350, and 500 mum. The optical design is based on a 2 m diameter telescope, providing a diffraction-limited resolution of 30 super(image ) at 250 mum. The gondola pointing system enables raster mapping of arbitrary geometry, with a repeatable positional accuracy of image30 super(image ); postflight pointing reconstruction to image5 super(image ) rms is achieved. The onboard telescope control software permits autonomous execution of a preselected set of maps, with the option of manual override. In this paper we describe the primary characteristics and measured in-flight performance of BLAST. BLAST performed a test flight in 2003 and has since made two scientifically productive long- duration balloon flights: a 100 hr flight from ESRANGE (Kiruna), Sweden to Victoria Island, northern Canada in 2005 June; and a 250 hr, circumpolar flight from McMurdo Station, Antarctica, in 2006 December.
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