The Lsm1-7/Pat1 complex binds to stress-activated mRNAs and modulates the response to hyperosmotic shock

RNA-binding proteins (RBPs) establish the cellular fate of a transcript, but an understanding of these processes has been limited by a lack of identified specific interactions between RNA and protein molecules. Using MS2 RNA tagging, we have purified proteins associated with individual mRNA species induced by osmotic stress, STL1 and GPD1. We found members of the Lsm1-7/Pat1 RBP complex to preferentially bind these mRNAs, relative to the non-stress induced mRNAs, HYP2 and ASH1. To assess the functional importance, we mutated components of the Lsm1-7/Pat1 RBP complex and analyzed the impact on expression of osmostress gene products. We observed a defect in global translation inhibition under osmotic stress in pat1 and lsm1 mutants, which correlated with an abnormally high association of both non-stress and stress-induced mRNAs to translationally active polysomes. Additionally, for stress-induced proteins normally triggered only by moderate or high osmostress, in the mutants the protein levels rose high already at weak hyperosmosis. Analysis of ribosome passage on mRNAs through co-translational decay from the 5' end (5P-Seq) showed increased ribosome accumulation in lsm1 and pat1 mutants upstream of the start codon. This effect was particularly strong for mRNAs induced under osmostress. Thus, our results indicate that, in addition to its role in degradation, the Lsm1-7/Pat1 complex acts as a selective translational repressor, having stronger effect over the translation initiation of heavily expressed mRNAs. Binding of the Lsm1-7/Pat1p complex to osmostress-induced mRNAs mitigates their translation, suppressing it in conditions of weak or no stress, and avoiding a hyperresponse when triggered

Source apportionment of PM 2.5 chemically speciated mass and particle number concentrations in New York City

The major sources of fine particulate matter (PM2.5) in New York City (NYC) were apportioned by applying positive matrix factorization (PMF) to two different sets of particle characteristics: mass concentrations using chemical speciation data and particle number concentrations (PNC) using number size distribution, continuously monitored gases, and PM2.5 data. Post-processing was applied to the PMF results to: (i) match with meteorological data, (ii) use wind data to detect the likely locations of the local sources, and (iii) use concentration weighted trajectory models to assess the strength of potential regional/transboundary sources. Nine sources of PM2.5 mass were apportioned and identified as: secondary ammonium sulfate, secondary ammonium nitrate, road traffic exhaust, crustal dust, fresh sea-salt, aged sea-salt, biomass burning, residual oil/domestic heating and zinc. The sources of PNC were investigated using hourly average number concentrations in six size bins, gaseous air pollutants, mass concentrations of PM2.5, particulate sulfate, OC, and EC. These data were divided into 3 periods indicative of different seasonal conditions. Five sources were resolved for each period: secondary particles, road traffic, NYC background pollution (traffic and oil heating largely in Manhattan), nucleation and O3-rich aerosol. Although traffic does not account for large amounts of PM2.5 mass, it was the main source of particles advected from heavily trafficked zones. The use of residual oil had limited impacts on PM2.5 mass but dominates PNC in cold periods

Analysis of major air pollutants and submicron particles in New York City and Long Island

A year-long sampling campaign of major air pollutants and submicron particle number size distributions was conducted at two sites taken as representative of city-wide air quality in New York City and Long Island, respectively. A number of species were quantified with hourly time resolution, including particle number concentrations in 6 size ranges (20-30 nm, 30-50 nm, 50-70 nm, 70-100 nm, 100-200 nm, and >200 nm), nitrogen oxides, sulfur dioxide, ozone, carbon monoxide, methane, non-methane hydrocarbons, PM2.5 mass concentration and some PM major components (sulfate, organic and elemental carbon). Hourly concentrations of primary and secondary organic carbon were estimated using the EC tracer method. Data were matched with weather parameters and air parcel back-trajectories. A series of tools were thus applied to: (i) study the seasonal, weekly, diurnal cycles of pollutants; (ii) investigate the relationships amongst pollutants through correlation and lagged correlation analyses; (iii) depict the role of atmospheric photochemical processes; (iv) examine the location of the potential sources by mean of conditional bivariate probability function analysis and (v) investigate the role of regional transport of air masses to the concentrations of analyzed species. Results indicate that concentrations of NOx, SO2, CO, non-methane hydrocarbons, primary OC and EC are predominantly determined by local sources, but are also affected by regional transports of polluted air masses. On the contrary, the transport of continental polluted air masses has a main effect in raising the concentrations of secondary PM2.5 (sulfate and secondary organic carbon). By providing direct information on the concentrations and trends of key pollutants and submicron particle number concentrations, this study finally enables some general considerations about air quality status and atmospheric processes over the New York City metropolitan area. (C) 2016 Elsevier Ltd. All rights reserved

LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression

RNA-binding proteins (RBPs) bind to and post-transcriptionally regulate the stability of mRNAs. La-related protein 1 (LARP1) is a conserved RBP that interacts with poly-A-binding protein and is known to regulate 5′-terminal oligopyrimidine tract (TOP) mRNA translation. Here, we show that LARP1 is complexed to 3000 mRNAs enriched for cancer pathways. A prominent member of the LARP1 interactome is mTOR whose mRNA transcript is stabilized by LARP1. At a functional level, we show that LARP1 promotes cell migration, invasion, anchorage-independent growth and in vivo tumorigenesis. Furthermore, we show that LARP1 expression is elevated in epithelial cancers such as cervical and non-small cell lung cancers, where its expression correlates with disease progression and adverse prognosis, respectively. We therefore conclude that, through the post-transcriptional regulation of genes such as mTOR within cancer pathways, LARP1 contributes to cancer progression