The nuclear chronicles: gene transcription and molecular traveling

1999 ◽  
Vol 77 (4) ◽  
pp. 243-247
Author(s):  
Carole Kretz-Remy ◽  
Sébastien Michaud ◽  
Robert M Tanguay
Keyword(s):  
Cell Biology ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Quebec City ◽  
Nuclear Pore ◽  
Rna Transport ◽  
Regulate Gene Expression ◽  
The Subject ◽  
Cytoplasmic Ribosomes ◽  
Rna Transcript

The transfer and processing of an RNA transcript from its locus of transcription on chromatin through the nuclear membrane to its site of translation on cytoplasmic ribosomes is a long and complex journey involving numerous processes and interactions with various macromolecules. These various steps that regulate gene expression were the subject of the 9th Winternational Symposium of the Canadian Society of Biochemistry and Molecular & Cell Biology held at Manoir du Lac Delage, a small resort centre north of Québec City on February 12-15, 1999.Key words: nuclear pore, RNA transport, chromatin, RNA-binding proteins, nucleoporins.

scholarly journals HIV-1 remodels the nuclear pore complex

2011 ◽  
Vol 193 (4) ◽  
pp. 619-631 ◽  
Author(s):  
Anne Monette ◽  
Nelly Panté ◽  
Andrew J. Mouland
Keyword(s):  
Nuclear Export ◽  
Cell Biology ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Immunogold Electron Microscopy ◽  
Nuclear Pore ◽  
Viral Control ◽  
Host Cell Proteins ◽  
Associated Proteins ◽  
Hiv 1

Human immunodeficiency virus type 1 (HIV-1) commandeers host cell proteins and machineries for its replication. Our earlier work showed that HIV-1 induced the cytoplasmic retention of nucleocytoplasmic shuttling and ribonucleic acid (RNA)–binding proteins. This retention is dependent on nuclear export of the viral genomic RNA and on changes in the localization and expression level of the nucleoporin (Nup) p62 (Nup62). To further characterize the extent of perturbation induced by HIV-1, we performed proteomics analyses of nuclear envelopes (NEs) isolated from infected T cells. Infection induced extensive changes in the composition of the NE and its associated proteins, including a remarkable decrease in the abundance of Nups. Immunogold electron microscopy revealed the translocation of Nups into the cytoplasm. Nup62 was identified as a component of purified virus, and small interfering RNA depletion studies revealed an important role for this Nup in virus gene expression and infectivity. This detailed analysis highlights the profound effects on NE composition induced by HIV-1 infection, providing further evidence of the magnitude of viral control over the cell biology of its host.

scholarly journals Musashi proteins are post-transcriptional regulators of the epithelial-luminal cell state

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Yarden Katz ◽  
Feifei Li ◽  
Nicole J Lambert ◽  
Ethan S Sokol ◽  
Wai-Leong Tam ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Biology ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
State Regulation ◽  
Ribosome Profiling ◽  
Luminal Cell ◽  
Mesenchymal Transition ◽  
Cell State

The conserved Musashi (Msi) family of RNA binding proteins are expressed in stem/progenitor and cancer cells, but generally absent from differentiated cells, consistent with a role in cell state regulation. We found that Msi genes are rarely mutated but frequently overexpressed in human cancers and are associated with an epithelial-luminal cell state. Using ribosome profiling and RNA-seq analysis, we found that Msi proteins regulate translation of genes implicated in epithelial cell biology and epithelial-to-mesenchymal transition (EMT), and promote an epithelial splicing pattern. Overexpression of Msi proteins inhibited the translation of Jagged1, a factor required for EMT, and repressed EMT in cell culture and in mammary gland in vivo. Knockdown of Msis in epithelial cancer cells promoted loss of epithelial identity. Our results show that mammalian Msi proteins contribute to an epithelial gene expression program in neural and mammary cell types.

scholarly journals RNA Motifs and Modification Involve in RNA Long-Distance Transport in Plants

2021 ◽  
Vol 9 ◽  
Author(s):  
Tao Wang ◽  
Xiaojun Li ◽  
Xiaojing Zhang ◽  
Qing Wang ◽  
Wenqian Liu ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Future Research ◽  
Rna Transport ◽  
Long Distance ◽  
Rna Motifs ◽  
Related Sequence ◽  
Long Distance Transport ◽  
Nucleotide Mutation ◽  
Distance Transport

A large number of RNA molecules have been found in the phloem of higher plants, and they can be transported to distant organelles through the phloem. RNA signals are important cues to be evolving in fortification strategies by long-distance transportation when suffering from various physiological challenges. So far, the mechanism of RNA selectively transportation through phloem cells is still in progress. Up to now, evidence have shown that several RNA motifs including Polypyrimidine (poly-CU) sequence, transfer RNA (tRNA)-related sequence, Single Nucleotide Mutation bound with specific RNA binding proteins to form Ribonucleotide protein (RNP) complexes could facilitate RNA mobility in plants. Furthermore, some RNA secondary structure such as tRNA-like structure (TLS), untranslation region (UTR) of mRNA, stem-loop structure of pre-miRNA also contributed to the mobility of RNAs. Latest researchs found that RNA methylation such as methylated 5′ cytosine (m5C) played an important role in RNA transport and function. These studies lay a theoretical foundation to uncover the mechanism of RNA transport. We aim to provide ideas and clues to inspire future research on the function of RNA motifs in RNA long-distance transport, furthermore to explore the underlying mechanism of RNA systematic signaling.

scholarly journals SAM68: Signal Transduction and RNA Metabolism in Human Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Paola Frisone ◽  
Davide Pradella ◽  
Anna Di Matteo ◽  
Elisa Belloni ◽  
Claudia Ghigna ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Signal Transduction ◽  
Nuclear Export ◽  
Cell Biology ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Splice Variants ◽  
Human Cancer ◽  
Rna Metabolism ◽  
Regulatory Sequences

Alterations in expression and/or activity of splicing factors as well as mutations incis-acting splicing regulatory sequences contribute to cancer phenotypes. Genome-wide studies have revealed more than 15,000 tumor-associated splice variants derived from genes involved in almost every aspect of cancer cell biology, including proliferation, differentiation, cell cycle control, metabolism, apoptosis, motility, invasion, and angiogenesis. In the past decades, several RNA binding proteins (RBPs) have been implicated in tumorigenesis. SAM68 (SRC associated in mitosis of 68 kDa) belongs to the STAR (signal transduction and activation of RNA metabolism) family of RBPs. SAM68 is involved in several steps of mRNA metabolism, from transcription to alternative splicing and then to nuclear export. Moreover, SAM68 participates in signaling pathways associated with cell response to stimuli, cell cycle transitions, and viral infections. Recent evidence has linked this RBP to the onset and progression of different tumors, highlighting misregulation of SAM68-regulated splicing events as a key step in neoplastic transformation and tumor progression. Here we review recent studies on the role of SAM68 in splicing regulation and we discuss its contribution to aberrant pre-mRNA processing in cancer.

scholarly journals KH domain containing RNA-binding proteins coordinate with microRNAs to regulate Caenorhabditis elegans development

2021 ◽  
Vol 11 (2) ◽  
Author(s):  
Dustin Haskell ◽  
Anna Zinovyeva
Keyword(s):  
Gene Expression ◽  
Caenorhabditis Elegans ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulate Gene Expression ◽  
C Elegans ◽  
Binding Domains ◽  
Kh Domain ◽  
Regulate Gene

Abstract MicroRNAs (miRNAs) and RNA-binding proteins (RBPs) regulate gene expression at the post-transcriptional level, but the extent to which these key regulators of gene expression coordinate their activities and the precise mechanisms of this coordination are not well understood. RBPs often have recognizable RNA binding domains that correlate with specific protein function. Recently, several RBPs containing K homology (KH) RNA binding domains were shown to work with miRNAs to regulate gene expression, raising the possibility that KH domains may be important for coordinating with miRNA pathways in gene expression regulation. To ascertain whether additional KH domain proteins functionally interact with miRNAs during Caenorhabditis elegans development, we knocked down twenty-four genes encoding KH-domain proteins in several miRNA sensitized genetic backgrounds. Here, we report that a majority of the KH domain-containing genes genetically interact with multiple miRNAs and Argonaute alg-1. Interestingly, two KH domain genes, predicted splicing factors sfa-1 and asd-2, genetically interacted with all of the miRNA mutants tested, whereas other KH domain genes showed genetic interactions only with specific miRNAs. Our domain architecture and phylogenetic relationship analyses of the C. elegans KH domain-containing proteins revealed potential groups that may share both structure and function. Collectively, we show that many C. elegans KH domain RBPs functionally interact with miRNAs, suggesting direct or indirect coordination between these two classes of post-transcriptional gene expression regulators.

scholarly journals I-KCKT allows dissection-free RNA profiling of adult Drosophila intestinal progenitor cells

2020 ◽  
Author(s):  
Kasun Buddika ◽  
Jingjing Xu ◽  
Ishara S. Ariyapala ◽  
Nicholas S. Sokol
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Protein Interactions ◽  
Cell Biology ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Stem Cell Population ◽  
Binding Motif ◽  
Rna Profiling ◽  
Adult Drosophila

AbstractThe adult Drosophila intestinal epithelium is a model system for stem cell biology, but its utility is limited by current biochemical methods that lack cell type resolution. Here, we describe a new proximity-based profiling method that relies upon a GAL4 driver, termed intestinal-kickout-GAL4 (I-KCKT-GAL4), exclusively expressed in intestinal progenitor cells. This method used UV cross-linked whole animal frozen powder as its starting material to immunoprecipitate the RNA cargoes of transgenic epitope-tagged RNA binding proteins driven by I-KCKT-GAL4. When applied to the general mRNA-binder, poly(A)-binding protein, the RNA profile obtained by this method identified 98.8% of transcripts found after progenitor cell sorting, and had low background noise despite being derived from whole animal lysate. We also mapped the targets of the more selective RNA binder, Fragile Mental Retardation Protein, using enhanced CLIP, and report for the first time its binding motif in Drosophila cells. This method will therefore enable the RNA profiling of wildtype and mutant intestinal progenitor cells from intact flies exposed to normal and altered environments, as well as the identification of RNA-protein interactions critical for stem cell function.Summary StatementWe report a dissection-free method to identify proximity-based RNA-protein interactions in an in vivo stem cell population, enabling molecular analysis of these cells at unprecedented speed and resolution.

scholarly journals Satellite DNA-containing gigantic introns in a unique gene expression program during Drosophila spermatogenesis

2018 ◽  
Author(s):  
Jaclyn M Fingerhut ◽  
Jessica V Moran ◽  
Yukiko Yamashita
Keyword(s):  
Gene Expression ◽  
Satellite Dna ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Gene Expression Program ◽  
Dna Repeats ◽  
Regulate Gene Expression ◽  
Unique Gene ◽  
Expression Of Genes ◽  
Expression Program

Intron gigantism, where genes contain megabase-sized introns, is observed across species, yet little is known about its purpose or regulation. Here we identify a unique gene expression program utilized for the proper expression of genes with intron gigantism. We find that two Drosophila genes with intron gigantism, kl-3 and kl-5, are transcribed in a spatiotemporal manner over the course of spermatocyte differentiation, which spans ~90 hours. The introns of these genes contain megabases of simple satellite DNA repeats that comprise over 99% of the gene loci, and these satellite-DNA containing introns are transcribed. We identify two RNA-binding proteins that specifically localize to kl-3 and kl-5 transcripts and are needed for the successful transcription or processing of these genes. We propose that genes with intron gigantism require a unique gene expression program, which may serve as a platform to regulate gene expression during cellular differentiation.

scholarly journals Differences in Vaccine and SARS-CoV-2 Replication Derived mRNA: Implications for Cell Biology and Future Disease

2021 ◽  
Author(s):  
Kevin McKernan ◽  
Anthony M. Kyriakopoulos ◽  
Peter McCullough
Keyword(s):  
Binding Sites ◽  
Cell Biology ◽  
Protein Production ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Codon Optimization ◽  
Synonymous Codon ◽  
Gc Content ◽  
Rna Sequences ◽  
G Quadruplex

Codon optimization describes the process used to increase protein production by use of alternative but synonymous codon changes. In SARS-CoV-2 mRNA vaccines codon optimizations can result in differential secondary conformations that inevitably affect a protein’s function with significant consequences to the cell. Importantly, when codon optimization increases the GC content of synthetic mRNAs, there can be an inevitable enrichment of G-quartets which potentially form G-quadruplex structures. The emerging G-quadruplexes are favorable binding sites of RNA binding proteins like helicases that inevitably affect epigenetic reprogramming of the cell by altering transcription, translation and replication. In this study, we performed a RNAfold analysis to investigate alterations in secondary structures of mRNAs in SARS-CoV-2 vaccines due to codon optimization. We show a significant increase in the GC content of mRNAs in vaccines as compared to native SARS-CoV-2 RNA sequences encoding the spike protein. As the GC enrichment leads to more G-quadruplex structure formations, these may contribute to potential pathological processes initiated by SARS-CoV-2 molecular vaccination.

scholarly journals Human Pumilio proteins directly bind the CCR4-NOT deadenylase complex to regulate the transcriptome

2020 ◽  
Author(s):  
Isioma I.I. Enwerem ◽  
Nathan D. Elrod ◽  
Chung-Te Chang ◽  
Ai Lin ◽  
Ping Ji ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Molecular Model ◽  
Direct Interaction ◽  
Vertebrate Development ◽  
Regulate Gene Expression ◽  
Mrna Decapping ◽  
Specific Mrnas ◽  
Decapping Enzyme ◽  
Pumilio Proteins

AbstractPumilio paralogs, PUM1 and PUM2, are sequence-specific RNA-binding proteins that are essential for vertebrate development and neurological functions. PUM1&2 negatively regulate gene expression by accelerating degradation of specific mRNAs. Here, we determined the repression mechanism and impact of human PUM1&2 on the transcriptome. We identified subunits of the CCR4-NOT (CNOT) deadenylase complex required for stable interaction with PUM1&2 and to elicit CNOT-dependent repression. Isoform-level RNA sequencing revealed broad co-regulation of target mRNAs through the PUM-CNOT repression mechanism.Functional dissection of the domains of PUM1&2 identified a conserved N-terminal region that confers the predominant repressive activity via direct interaction with CNOT. In addition, we show that the mRNA decapping enzyme, DCP2, has an important role in repression by PUM1&2 N-terminal regions. Our results support a molecular model of repression by human PUM1&2 via direct recruitment of CNOT deadenylation machinery in a decapping-dependent mRNA decay pathway.

scholarly journals Loss of nucleoporin Nup50 is a risk factor for amyotrophic lateral sclerosis

2021 ◽  
Author(s):  
Salim Megat ◽  
Natalia Mora ◽  
Jason Sanogo ◽  
Alberto Catanese ◽  
Najwa Ouali ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Association Studies ◽  
Nuclear Pore ◽  
Genome Wide Association Studies ◽  
Gene Encoding ◽  
Pathogenic Variants ◽  
Or Gene ◽  
Lateral Sclerosis

The genetic basis of amyotrophic lateral sclerosis (ALS) is still incompletely understood. Using two independent genetic strategies, we show here that a large part of ALS heritability lies in genes expressed in inhibitory and excitatory neurons, especially at splicing sites regulated by a defined set of RNA binding proteins including TDP-43 and FUS. We conducted a transcriptome wide association study (TWAS) and identified 59 loci associated with ALS, including 14 previously identified genes, some of them not previously reaching significance in genome wide association studies. Among the 45 novel genes, several genes are involved in pathways known to be affected in ALS such as mitochondrial metabolism (including ATP5H, ATP5D, BCS1L), proteostasis (including COPS7A, G2E3, TMEM175, USP35) or gene expression and RNA metabolism (including ARID1B, ATXN3, PTBP2, TAF10). Interestingly, decreased expression of NUP50, a constrained gene encoding a nuclear pore basket protein, was associated with ALS in TWAS (Zscore = -4, FDR = 0.034). 11 potentially pathogenic variants (CADD score > 20) in 23 patients were identified in the NUP50 gene, most of them in the region of the protein mediating interaction with Importin alpha, and including 2 frameshift mutations. In cells from two patients carrying NUP50 variants, we showed decreased levels of NUP50 protein. Importantly, knocking down Nup50 led to increased neuronal death associated with p62 and nucleoporin inclusions in cultured neurons, and motor defects in Drosophila and zebrafish models. In all, our study identifies alterations in splicing in neurons as a critical pathogenic process in ALS, uncovers several new loci potentially contributing to ALS missing heritability, and provides genetic evidence linking nuclear pore defects to ALS.

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