Design, synthesis and DNA/RNA binding studies of nucleic acids comprising stereoregular and acyclic polycarbamate backbone: polycarbamate nucleic acids (PCNA)

2010 ◽  
Vol 8 (16) ◽  
pp. 3734 ◽  
Author(s):  
Vangala Madhuri ◽  
Vaijayanti A. Kumar
Keyword(s):  
Nucleic Acids ◽  
Rna Binding ◽  
Binding Studies ◽  
Design Synthesis

Conformationally restricted cationic polyamide analogs of nucleic acids: Design, synthesis, and DNA/RNA binding studies

2004 ◽  
Vol 76 (7-8) ◽  
pp. 1599-1603 ◽  
Author(s):  
V. A. Kumar ◽  
Moneesha D'Costa ◽  
P. S. Lonkar ◽  
P. S. Pallan ◽  
K. N. Ganesh ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Water Solubility ◽  
Rna Binding ◽  
Binding Studies ◽  
Design Synthesis ◽  
Conformationally Restricted ◽  
Nucleic Acid Analogs ◽  
Conformational Preferences

The remarkable medicinal importance of the achiral, acyclic, and uncharged aminoethylglycyl peptide nucleic acids (aegPNAs) as DNA/RNA mimics has challenged chemists to circumvent the limitations of their in vivo efficacy. In this context, we have designed conformationally restricted five- and six-membered cyclic PNA analogs by introduction of chemical bridges in aegPNAs leading to a large variety of structures with defined configurations and conformational preferences, effecting concomitant installation of a positive charge in the backbone. The synthesis and biophysical properties of these cationic aminoethylprolyl PNAs, pyrrolidine PNAs, and piperidine PNAs endowed with increased water solubility and affinity toward target nucleic acids is presented. These nucleic acid analogs as lead structures are a part of a chemical evolution process that might give rise to a synthetic nucleic acid analog having optimum properties for medicinal applications.

scholarly journals Synthetic, Structural, and RNA Binding Studies on 2‐Aminopyridine‐Modified Triplex‐Forming Peptide Nucleic Acids

2019 ◽  
Vol 25 (17) ◽  
pp. 4367-4372 ◽  
Author(s):  
Venubabu Kotikam ◽  
Scott D. Kennedy ◽  
James A. MacKay ◽  
Eriks Rozners
Keyword(s):  
Nucleic Acids ◽  
Rna Binding ◽  
Peptide Nucleic Acids ◽  
Binding Studies

scholarly journals Novel Compounds Targeting the RNA-Binding Protein HuR. Structure-Based Design, Synthesis, and Interaction Studies

2019 ◽  
Vol 10 (4) ◽  
pp. 615-620 ◽  
Author(s):  
Serena Della Volpe ◽  
Rita Nasti ◽  
Michele Queirolo ◽  
M. Yagiz Unver ◽  
Varsha K. Jumde ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Design Synthesis ◽  
Interaction Studies

NAB2: a yeast nuclear polyadenylated RNA-binding protein essential for cell viability

1993 ◽  
Vol 13 (5) ◽  
pp. 2730-2741 ◽  
Author(s):  
J T Anderson ◽  
S M Wilson ◽  
K V Datar ◽  
M S Swanson
Keyword(s):  
Rna Binding ◽  
Uv Light ◽  
Polyclonal Antibodies ◽  
Yeast Cells ◽  
Binding Studies ◽  
Single Stranded Dna ◽  
Binding Motifs ◽  
Polyadenylated Rna ◽  
Nuclear Rna

A variety of nuclear ribonucleoproteins are believed to associate directly with nascent RNA polymerase II transcripts and remain associated during subsequent nuclear RNA processing reactions, including pre-mRNA polyadenylation and splicing as well as nucleocytoplasmic mRNA transport. To investigate the functions of these proteins by using a combined biochemical and genetic approach, we have isolated nuclear polyadenylated RNA-binding (NAB) proteins from Saccharomyces cerevisiae. Living yeast cells were irradiated with UV light to covalently cross-link proteins intimately associated with RNA in vivo. Polyadenylated RNAs were then selectively purified, and the covalent RNA-protein complexes were used to elicit antibodies in mice. Both monoclonal and polyclonal antibodies which detect a variety of NAB proteins were prepared. Here we characterize one of these proteins, NAB2. NAB2 is one of the major proteins associated with nuclear polyadenylated RNA in vivo, as detected by UV light-induced cross-linking. Cellular immunofluorescence, using both monoclonal and polyclonal antibodies, demonstrates that the NAB2 protein is localized within the nucleus. The deduced primary structure of NAB2 indicates that it is composed of at least two distinct types of RNA-binding motifs: (i) an RGG box recently described in a variety of heterogeneous nuclear RNA-, pre-rRNA-, mRNA-, and small nucleolar RNA-binding proteins and (ii) CCCH motif repeats related to the zinc-binding motifs of the largest subunit of RNA polymerases I, II, and III. In vitro RNA homopolymer/single-stranded DNA binding studies indicate that although both the RGG box and CCCH motifs bind poly(G), poly(U), and single-stranded DNA, the CCCH motifs also bind to poly(A). NAB2 is located on chromosome VII within a cluster of ribonucleoprotein genes, and its expression is essential for cell growth.

Targeting of transcripts encoding membrane proteins in polarized epithelia: RNA–protein binding studies of the SGLT1 3′-UTR

2008 ◽  
Vol 36 (3) ◽  
pp. 525-527 ◽  
Author(s):  
Christopher M. Pedder ◽  
Dianne Ford ◽  
John E. Hesketh
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Localization ◽  
Complex Structure ◽  
Mrna Translation ◽  
Drosophila Embryo ◽  
Binding Studies ◽  
Polarized Epithelia ◽  
Apical Localization

mRNA stability, mRNA translation and spatial localization of mRNA species within a cell can be governed by signals in the 3′-UTR (3′-untranslated region). Local translation of proteins is essential for the development of many eukaryotic cell types, such as the Drosophila embryo, where the spatial and temporal localization of bicoid and gurken mRNAs, among others, is required to establish morphogen gradients. More recent studies have suggested that mRNA localization also occurs with transcripts coding for membrane-based or secreted proteins, and that localization at organelles such as the endoplasmic reticulum directs translation more efficiently to specific subdomains, so as to aid correct protein localization. In human epithelial cells, the mRNA coding for SGLT1 (sodium–glucose co-transporter 1), an apical membrane protein, has been shown to be localized apically in polarized cells. However, the nature of the signals and RNA-binding proteins involved are unknown. Ongoing work is aimed at identifying the localization signals in the SGLT1 3′-UTR and the corresponding binding proteins. Using a protein extract from polarized Caco-2 cells, both EMSAs (electrophoretic mobility-shift assays) and UV cross-linking assays have shown that a specific protein complex is formed with the first 300 bases of the 3′-UTR sequence. MFold predictions suggest that this region folds into a complex structure and ongoing studies using a series of strategic deletions are being carried out to identify the precise nature of the motif involved, particularly the role of the sequence or RNA secondary structure, as well as to identify the main proteins present within the complex. Such information will provide details of the post-transcriptional events that lead to apical localization of the SGLT1 transcript and may reveal mechanisms of more fundamental importance in the apical localization of proteins in polarized epithelia.

scholarly journals Structural basis underlying CAC RNA recognition by the RRM domain of dimeric RNA-binding protein RBPMS

2015 ◽  
Vol 49 ◽  
Author(s):  
Marianna Teplova ◽  
Thalia A. Farazi ◽  
Thomas Tuschl ◽  
Dinshaw J. Patel
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Hek293 Cells ◽  
Structural Basis ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Binding Studies ◽  
Muscle Plasticity ◽  
Rrm Domain

AbstractRNA-binding protein with multiple splicing (designated RBPMS) is a higher vertebrate mRNA-binding protein containing a single RNA recognition motif (RRM). RBPMS has been shown to be involved in mRNA transport, localization and stability, with key roles in axon guidance, smooth muscle plasticity, as well as regulation of cancer cell proliferation and migration. We report on structure-function studies of the RRM domain of RBPMS bound to a CAC-containing single-stranded RNA. These results provide insights into potential topologies of complexes formed by the RBPMS RRM domain and the tandem CAC repeat binding sites as detected by photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation. These studies establish that the RRM domain of RBPMS forms a symmetrical dimer in the free state, with each monomer binding sequence-specifically to all three nucleotides of a CAC segment in the RNA bound state. Structure-guided mutations within the dimerization and RNA-binding interfaces of RBPMS RRM on RNA complex formation resulted in both disruption of dimerization and a decrease in RNA-binding affinity as observed by size exclusion chromatography and isothermal titration calorimetry. As anticipated from biochemical binding studies, over-expression of dimerization or RNA-binding mutants of Flag-HA-tagged RBPMS were no longer able to track with stress granules in HEK293 cells, thereby documenting the deleterious effects of such mutations in vivo.

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