SMN interacts with a novel family of hnRNP and spliceosomal proteins

Spinal muscular atrophy (SMA) is a common neurodegenerative disease caused by deletion or loss-of-function mutations of the survival of motor neurons (SMN) protein. SMN is in a complex with several proteins, including Gemin2, Gemin3 and Gemin4, and it plays important roles in small nuclear ribonucleoprotein (snRNP) biogenesis and in pre-mRNA splicing. Here, we characterize three new hnRNP proteins, collectively referred to as hnRNP Qs, which are derived from alternative splicing of a single gene. The hnRNP Q proteins interact with SMN, and the most common SMN mutant found in SMA patients is defective in its interactions with them. We further demonstrate that hnRNP Qs are required for efficient pre-mRNA splicing in vitro. The hnRNP Q proteins may provide a molecular link between the SMN complex and splicing.     

Site-specific crosslinking of human microRNPs to RNA targets

MicroRNAs (miRNAs) regulate the expression of numerous genes and are implicated in the pathogenesis of many human diseases. miRNAs act as specificity determinants to guide deposition of microRNPs (miRNPs) onto miRNA recognition elements (MREs) that are found in mRNA targets. We have adapted a site-specific crosslinking approach, previously used in the analysis of splicing, to interrogate protein factors that physically associate with MREs in human cells. We find that Ago proteins are the only proteins that bind to the MRE in a miRNA-dependent manner. Our method may be used in various experimental systems to analyze protein factors that influence MRE accessibility by miRNAs and the composition of MRE-bound miRNPs.     

Synthesis and cytogenetic studies of structure--biological activity relationship of esters of Hecogenin and aza-homo-Hecogenin with N,N-bis(2-chloroethyl)aminocinnamic acid isomers

The esters of Hecogenin and aza-homo-Hecogenin with N,N-bis(2-chloroethyl)aminocinnamic acid isomers have been prepared and their cytogenetic studies of structure-biological activity relationship were evaluated. The cytogenetic effects (sister chromatid exchanges (SCEs) induction and proliferation rate indices (PRIs) depression) by o-, m- and p-[N,N-bis(2-chloroethyl)amino] cinnamic acid were also investigated. Among the above compounds tested, those of the m-[N,N-bis(2-chloroethyl)amino] cinnamic acid and of the o-[N,N-bis(2-chloroethyl)amino] cinnamic acid ester of aza-homo-Hecogenin were more active in comparison to the others.     

Mitochondrial protein BmPAPI modulates the length of mature piRNAs

PIWI proteins and their associated PIWI-interacting RNAs (piRNAs) protect genome integrity by silencing transposons in animal germlines. The molecular mechanisms and components responsible for piRNA biogenesis remain elusive. PIWI proteins contain conserved symmetrical dimethylarginines (sDMAs) that are specifically targeted by TUDOR domain-containing proteins. Here we report that the sDMAs of PIWI proteins play crucial roles in PIWI localization and piRNA biogenesis in Bombyx mori-derived BmN4 cells, which harbor fully functional piRNA biogenesis machinery. Moreover, RNAi screenings for Bombyx genes encoding TUDOR domain-containing proteins identified BmPAPI, a Bombyx homolog of Drosophila PAPI, as a factor modulating the length of mature piRNAs. BmPAPI specifically recognized sDMAs and interacted with PIWI proteins at the surface of the mitochondrial outer membrane. BmPAPI depletion resulted in 3′-terminal extensions of mature piRNAs without affecting the piRNA quantity. These results reveal the BmPAPI-involved piRNA precursor processing mechanism on mitochondrial outer membrane scaffolds.     

Synthesis,characterization, toxicity,cytogenetic and in vivo antitumor studies of 1,1-dithiolate Cu(II) complexes with di-, tri-, tetra- amines and 1,3-thiazoles. Structure–activity correlation

A series of new mixed-ligand neutral copper(II) complexes of the general type [Cu(amine)(i-MNT)] and [Cu(tz)(i-MNT)] was prepared and characterized by elemental, spectroscopic methods, μ_eff, Λ_μ measurements and molecular modeling studies. The acute toxicity, the cytogenetic and the in vivo antitumor activity of the new complexes, is related to their chemical and physicochemical properties. Among the Cu(II) compounds tested the complex with 2-amino-5-methyl thiazole increases significantly the life span of leukemia P388 bearing mice in vivo.     

Post-transcriptional regulation of antiviral gene expression by N6-methyladenosine

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Diel patterns of zooplankton grazing in a shallow lake

A diel survey of in situ species-specific zooplankton clearancerates (with radioactively labelled Chlorella cells) was conductedin the shallow lake of Cr?teil characterized by small-sizedplanktonic forms (algae<10µm and zooplankton <1.3mm). Experiments were performed every 4h at two depths (1 and4m). Power functions relating individual filtering rates tobody length were established for the three most abundant cladoceransand for calanoids (nauplii being included in this feeding group),for each depth and time. No filtering penodicity was observedin Ceriodaphnia spp., adults and copepodites of Eudiaptomusgracilis and Eurytemora velox, and nauplii. On the contrary,clear nocturnal filtering peaks were obtained for Daphnia spp.and for Diaphanosoma brachyurum, these being more pronouncedfor the larger individuals at 1 m deep. The observed diel periodicitycannot be explained by variations in physico-chemical parametersor food concentration alone. The ecological significance ofthis phenomenon in the polymictic lake of Cr?teil is discussedin the light of previously published data and the hypothesesaccounting for it.