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Control of Stable RNA Synthesis

Melanie M. Barker and Richard L. Gourse

Transcription of rRNA is the ratelimiting step in ribosome production. In rapidly dividing Escherichia coli, ribosome synthesis represents the single largest expenditure of biosynthetic energy. At the fastest growth rates, over 70% of all transcription derives from the s...

Coupling Transcription and Alternative Splicing

Alberto R. Kornblihtt

Alternative splicing regulation not only depends on the interaction of splicing factors with splicing enhancers and silencers in the pre‑mRNA, but also on the coupling between transcription and splicing. This coupling is possible because splicing is often cotranscriptional and promoter identit...

Crystal Structures of the Ribosome and Ribosomal Subunits

Brian T. Wimberly

Efforts to understand the structural basis for translational mechanisms have long been hampered by the low resolution of ribosome structures. This impasse suddenly and dramatically changed in 2000 as a result of the determination of crystal structures of entire ribosomes and of ribosomal subun...

Cysteinyl-tRNA Synthetases

Ya-Ming Hou and John J. Perona

Biochemical, biophysical and molecular genetics studies of cysteinyl-tRNA synthetase have provided substantial insights into the catalytic properties of this important enzyme. High-resolution structure determination by X-ray crystallography, together with spectroscopic experiments, establish tha...

Dosage Compensation in Drosophila: A Ribonucleoprotein Complex Mediates Transcriptional Up-Regulation

Dianne Kindel and Hubert Amrein

Sex-specific chromosomes (commonly referred to as X and Y) provide the basis for sex determination in many animal species. However, this difference in karyotype has drastic consequences for the quantitative set-up of the genome of the two sexes, as sex chromosomes harbor thousands of genes with n...

Dynamics of Nucleolar Components

Thierry Cheutin, Tom Misteli and Miroslav Dundr

The nucleolus is one of the best-characterized cellular organelles. Its large physical size facilitated its early discovery and led to its detailed morphological description.1-3 The essential role of the nucleolus in ribosome biogenesis has encouraged extensive functional studies and to date t...

Encapsulation of Tobramycin and Neomycin B within Similar RNA Aptamer Binding

Licong Jiang and Dinshaw J. Patel

Aminoglycoside antibiotics are polycationic saccharides that exhibit therapeutic potential against bacterial infections. Functionally they interfere with translation and induce bacterial cell death through site-specific targeting of ribosomal 16S RNA.13 Further, the catalyt...

Endogenous Substrates of the Yeast NMD Pathway

Feng He and Allan Jacobson

The existence of a pathway that promotes rapid decay of nonsense-containing mRNAs raises the question of whether the substrates of this pathway are restricted to aberrant mRNAs. Additional substrates were sought by identifying mRNAs that were selectively stabilized in strains harboring mutations...

Exploiting RNA as a Therapeutic Target

Catherine D. Prescott

The emergence of drug resistant bacteria pose an everincreasing therapeutic problem. Although there are many resistance mechanisms, these can be broadly classified into three catergories.1,2 Firstly, antibiotics may be unable to reach susceptible target sites as a result of...

Features of Nonsense-Mediated mRNA Decay in Saccharomyces cerevisiae

Kristian E. Baker and Roy Parker

Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved cellular mechanism that reduces errors in eukaryotic gene expression by eliminating mRNAs that undergo aberrant translation termination. Two processes must be implemented for NMD to be achieved: recognition of an mRNA as ‘aberrant’, a...

Fluorescence-Signaling Nucleic Acid-Based Sensors

Razvan Nutiu, Lieven P. Billen and Yingfu Li

It is widely known that two single-stranded nucleic acids with complementary sequences have the inherent ability to form Watson-Crick duplex structures. The simplicity and sequence-specificity of duplex structure formation, the high chemical stability of a duplex, and the convenience of automated...

Functional and Mechanistic Insights From Genome‑Wide Studies of Splicing Regulation in the Brain

Jernej Ule and Robert B. Darnell

We review here results arising from the systematic functional analysis of Nova, a neuron‑specific RNA binding protein targeted in an autoimmune neurological disorder associated with cancer. We have developed a combination of biochemical, genetic and bioinformatic methods to generate a global u...

Glutaminyl-tRNA Synthetases

John J. Perona

Extensive studies of E. coli glutaminyl-tRNA synthetase (GlnRS) over a greater than 30-year period have established this enzyme as an important paradigm for the class I tRNA synthetases. The later work in particular is distinguished by the interplay of genetic and biochemical experiments with a...

Glutamyl-tRNA Synthetases

Daniel Y. Dubois, Jacques Lapointe and Shun-ichi Sekine

Glutamyl-tRNA synthetase (GluRS) (EC 6.1.1.17), a class I aminoacyl-tRNA synthetase (aaRS), is primarily responsible for the glutamylation of tRNAGlu. It is part of the “minimal set” of seventeen aaRSs found in every living organism and its presence is essential for the viability of the cells, ...

Glycyl-tRNA Synthetase

Kiyotaka Shiba

Analysis of the sequence of GlyRS has yielded two surprising findings. The first is the existence of two mutually exclusive types of GlyRS. Although class-specific motifs indi cate both to be Class II enzymes, their overall lack of sequence similarity indicates they evolved from separate ancest...

Histidyl-tRNA Synthetases

Chris Francklyn and John Arnez

Histidyl-tRNA synthetase (HisRS) is the dimeric class IIa aminoacyl tRNA synthetase (aaRS) that joins histidine to tRNAHis. At a molecular weight in the range of 45 to 55 kDa, it is one of the smallest aaRS. Historical interest in HisRS is related to its involvement in the control of histidine b...

hnRNP Proteins and Splicing Control

Rebeca Martinez-Contreras, Philippe Cloutier, Lulzim Shkreta, Jean‑François Fisette, Timothée Revil and Benoit Chabot

Proteins of the heterogeneous nuclear ribonucleoparticles (hnRNP) family form a structurally diverse group of RNA binding proteins implicated in various functions in metazoans. Here we discuss recent advances supporting a role for these proteins in precursor‑messenger RNA (pre‑mRNA) spli...

Human Upf Proteins in NMD

Guramrit Singh and Jens Lykke-Andersen

The human Upf (hUpf) proteins work at the core of the nonsense-mediated mRNA decay (NMD) pathway. The three hUpf proteins, hUpf1, hUpf2 and hUpf3, form the hUpf complex, which is critical for the recognition and degradation of mRNAs containing premature termination codons (PTCs). The recognition o...

In vitro Tools and in vivo Engineering: Incorporation of Unnatural Amino Acids into Proteins

Thomas J. Magliery, Miro Pastrnak, J. Christopher Anderson, Stephen W. Santoro, Brad Herberich, Eric Meggers, Lei Wang and Peter G. Schultz

Unnatural protein mutagenesis has dramatically enhanced our ability to probe the basis of structure and function in protein biochemistry and has enabled us to create proteins with entirely novel properties. Recent advances in in vitro unnatural amino acid incorporation have expanded the ...

Inhibition of RNase P Processing

Leif A. Kirsebom and Anders Virtanen

The tRNA genes in all organisms studied so far are transcribed as precursors that have to be processed to generate biologically functional tRNA molecules. RNase P is an endoribonuclease that is essential for cell survival, and it is responsible for the maturation of the 5'termini of tRNA...

Inhibitors of Aminoacyl-tRNA Synthetases as Antibiotics and Tools for Structural and Mechanistic Studies

Robert Chênevert, Stéphane Bernier and Jacques Lap

Aminoacyl-tRNA synthetases (aaRS) catalyze the esterification of a particular tRNA with its corresponding amino acid. In the first reaction step, the appropriate amino acid is recognized by the enzyme and reacts with ATP to form an enzyme-bound mixed anhydride; in the second step, thi...

Inhibitors of Group I Intron Splicing

Iris Hoch, Christina Waldsich, and Renée Schroeder

Group I introns are intervening sequences which disrupt rRNA, tRNA or mRNAencoding genes. They are mainly found in mitochondrial and chloroplast genomes, in phage genomes and in the nuclear rDNA of lower eukaryotes.1 They are attractive targets for therapeutics because they...

Introduction

Mark O.J. Olson

The nucleolus is the most prominent structure in the nucleus of a cell observed by light or electron microscopy. In cells as in other aspects of life, the level of visibility usually depends on the importance of the job to be performed. Actively dividing cells have an enormous demand for proteins an...

Introns and Noncoding RNAs: The Hidden Layer of Eukaryotic Complexity

John S. Mattick

Although it is not yet widely appreciated by the molecular biological community, the vast majority of the transcriptional output of the genomes of the higher organisms is noncoding RNA, composed of introns spliced out from protein-coding transcripts, and separate noncoding RNA transcripts that ar...

Isoleucyl-tRNA Synthetases

Brian E. Nordin and Paul Schimmel

Isoleucyl-tRNA synthetase (IleRS) is an essential component of the protein biosynthetic machinery in living cells. All known examples are large, monomeric class I aminoacyltRNA synthetases (aaRSs). IleRS displays a well-defined and modular domain architecture consisting largely of an N-terminal ...


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