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The various factors involved in the global and transcript-specific mRNA export pathways in metazoans are analyzed. These factors associate with polysomes and facilitate the mRNA transport.

The changes in nuclear organization accompanying stimulus by the mating pheromone alpha factor of the Saccharomyces cerevisiae is examined. The results reveal RNA- and DNA-dependent determinants of nuclear organization and a detailed picture of how an entire chromosome alters its spatial conformation in response to a developmental cue.

In order to understand gene expression's pathways, properties and behaviors as a system, their processes are increasingly studied from global perspectives. The beginnings of mRNA-protein (mRNP) systems biology, as they have emerged from large-scale investigation of mRNP components, interactions and dynamics are reviewed.

Messenger RNAs (mRNAs) have been found to be recruited for nuclear export during transcription. In studying Np13 and mRNA export, mutations in Np13 and TATA-binding protein, combined, block mRNA export.

The Ran-GTPase cycle and certain nucleoporins necessary for export from the nucleus of the small ribosomal subunit are discussed. Information is based on a study using the cytoplasmic localization of the 5' ITS1 fragment as indicator for the export of the small ribosomal subunit to identify necessary genes. Mutations in Ran or its regulators cause 5' ITS1 to accumulate in the nucleoplasm. Accumulation of 5' ITS1 in the nucleus was not found in 28 yeast strains with mutations in other genes that affect traffic in the nucleus.

Uncoupling of the hnRNP Np13p, the main mRNA-binding protein of Saccharomyces cerevisiae, from mRNAs in stress-induced inhibition of mRNA export is discussed. Data that point to an export-incompetent RNP complex without Np13p as the reason for constituitively exported mRNAs' not leaving the nucleus in stressed cells are presented based on seeing that Np13p is exported from the nucleus after onset of strees while mRNA stays nuclear.

An in vivo nuclear export assay has been used to study arginine methylation for nuclear export of the heterogeneous nuclear ribonucleoproteins (hnRNPs). Various hnRNPs help in eukaryotic mRNA processing/export. Both Np13p and Hrp1p fail to leave the nucleus in cells without Hmt1p. Overexpression of Hmt1p helps in Np13p export. A genetic relationship exists between Mnt1p and cap-binding protein 80 (CBP80). Arginine methylation helps in nuclear export of hnRNP proteins. That is at least one of its biological roles. In Saccharomyces cerevisiae, the enzyme mainly responsible for arginine methylation is Hmt1p.

HIV-1 Vpr is similar to importin-B in the function in performs during HIV-1 nuclear import. This function is an essential part of the Vpr role in macrophage infection although not crucial for G2 arrest. The two functions of Vpr are genetically separable. When Vpr does not localize to the nuclear envelope HIV-1 cannot infect macrophages effectively.

A study was conducted to examine the correlation between the mammalian nuclear pore and the human genome by generating high-resolution, chromosome-wide binding maps of human nucleoporin 93 (Nup93) in the presence and absence of a potent histone deacetylase inhibitor (HDACI). Results showed that inhibition of HDACs lead to significant changes in genomic organization, recruiting regions of transcriptional regulation to mammalian nuclear pore complexes.

The paper presents a rational design of cellular memory in yeast by set of transcriptional activators. Measured quantitative parameters specify eukaryotic regulatory networks.

The discovery of four new factors required for mRNA export through a screen of all annotated nonessential Saccharomyces cerevisiae genes is reported. Results demonstrate coupling of mRNA surveillance to mRNA export and suggest specificity of the RNA surveillance machinery for different transcript populations.

Hmt1 is recruited during the beginning of the transcriptional elongation process. The research data suggest a model whereby Hmt1 affects transcriptional elongation and influences recruitment of RNA-processing factors.

Research has been conducted on messenger RNA export factors. The authors demonstrate that RNA polymerase II transcription can recruit Saccharomyces cerevisiae protein Npl3 to a gene independent of RNA sequence.

Differential responses to stimuli can affect how cells succumb to disease. In yeast, DNA damage can create heterogeneous responses. To delineate how a response contributes to a cell's future behavior, we constructed a transcription-based memory circuit that detects DNA repair to isolate subpopulations with heritable damage responses. Strongly responsive cells show multigenerational effects, including growth defects and iron-associated gene expression. Less-responsive cells exhibit increased mutation frequencies but resume wild-type behavior. These two subpopulations remain distinct for multiple generations, indicating a transmissible memory of damage. Collectively, this work demonstrates the efficacy of using synthetic biology to define how environmental exposure contributes to distinct cell fates. [ABSTRACT FROM AUTHOR]

Polyglutamine-binding protein 1 (PQBP1) is a highly conserved protein associated with neurodegenerative disorders. Here, we identify PQBP1 as an alternative messenger RNA (mRNA) splicing (AS) effector capable of influencing splicing of multiple mRNA targets. PQBP1 is associated with many splicing factors, including the key U2 small nuclear ribonucleoprotein (snRNP) component SF3B1 (subunit 1 of the splicing factor 3B [SF3B] protein complex). Loss of functional PQBP1 reduced SF3B1 substrate mRNA association and led to significant changes in AS patterns. Depletion of PQBP1 in primary mouse neurons reduced dendritic outgrowth and altered AS of mRNAs enriched for functions in neuron projection development. Disease-linked PQBP1 mutants were deficient in splicing factor associations and could not complement neurite outgrowth defects. Our results indicate that PQBP1 can affect the AS of multiple mRNAs and indicate specific affected targets whose splice site determination may contribute to the disease phenotype in PQBP1-linked neurological disorders. [ABSTRACT FROM AUTHOR]

Multidimensional cancer genome analysis and validation has defined Quaking (QKI), a member of the signal transduction and activation of RNA (STAR) family of RNA-binding proteins, as a novel glioblastoma multiforme (GBM) tumor suppressor. Here, we establish that p53 directly regulates QKI gene expression, and QKI protein associates with and leads to the stabilization of miR-20a; miR-20a, in turn, regulates TGFβR2 and the TGFβ signaling network. This pathway circuitry is substantiated by in silico epistasis analysis of its components in the human GBM TCGA (The Cancer Genome Atlas Project) collection and by their gain- and loss-of-function interactions in in vitro and in vivo complementation studies. This p53–QKI–miR-20a–TGFβ pathway expands our understanding of the p53 tumor suppression network in cancer and reveals a novel tumor suppression mechanism involving regulation of specific cancer-relevant microRNAs. [ABSTRACT FROM AUTHOR]

Establishment and maintenance of silent chromatin in the Saccharomyces cerevisiae involves a step-wise assembly of the SIR complex. Here we demonstrate a role for the protein arginine methyltransferase Hmt1 in this process. In the absence of catalytically active Hmt1, yeast cells display increased transcription from silent chromatin regions and increased mitotic recombination within tandem repeats of rDNA. At the molecular level, loss of Hmt1's catalytic activity results in decreased Sir2 and dimethylated Arg-3 histone H4 occupancy across silent chromatin regions. These data suggest a model whereby protein arginine methylation affects the establishment and maintenance of silent chromatin. [ABSTRACT FROM AUTHOR]