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Adapt Gene RNA Transcripts as Riboregulators

Dana Crawford and Kelvin J. A. Davies

There is growing interest in the study of so-called riboregulator or non-coding RNAs. These spliced and polyadenylated RNAs contain either a very short or no apparent open reading frame or translational product. However, they are associated with a wide range of biological activities that...

Xist RNA Associates with Chromatin and Causes Gene Silencing

Anton Wutz

The mammalian Xist gene produces a long, spliced and poly-adenylated noncoding RNA that is uniquely distributed in the nucleus. Xist RNA spreads in cis from its site of transcription over the entire X-chromosome and mediates X-inactivation, the transitional silencing of one of the two X-chromosom...

Accuracy of Aminoacyl-tRNA Synthetases: Proofreading of Amino Acids

Hieronim Jakubowski

Fundamental to the function of living cells is the accurate processing of genetic information. Aminoacyl-tRNA synthetases participate in the processing of genetic information by faithfully matching amino acids with their cognate tRNAs, thereby maintaining the rules of the genetic code. When differe...

Alanyl-tRNA Synthetases

Lluis Ribas de Pouplana, Karin Musier-Forsyth and Paul Schimmel

Alanyl-tRNA synthetases (AlaRS) catalyze the aminoacy- lation of tRNAAla and thereby establish the connection between alanine and its codons, according to the algorithm of the genetic code.1 This reaction takes place in two steps catalyzed by a single active site. First, alanine is activated ...

All Termination Events Are Not Equal: Premature Termination in Yeast Is Aberrant and Triggers NMD

Nadia Amrani and Allan Jacobson

Nonsense-mediated mRNA decay (NMD) is triggered by premature translation termination, but the features distinguishing that event from normal termination are unknown. One model for NMD in yeast suggests that decay-inducing factors bound to mRNA during early processing events are routinely removed...

Allosteric Ribozymes As Molecular Sensors and Genetic Regulatory Switches

Garrett A. Soukup

Since the discovery of RNA catalysts, biotechnology has focused heavily on utilizing ribozymes as reagents to control RNA processing and gene expression. However, ribozymes can also be manipulated to report events that affect their folding and catalysis. As with protein enzymes, ribozyme activ...

Alternative Splicing in Disease

James P. Orengo and Thomas A. Cooper

Alternative splicing is a major source of diversity in the human proteome. The regulation of alternative splicing modulates the composition of this diversity to fulfill the physiological requirements of a cell. When control of alternative splicing is disrupted, the result can be a failure to meet ce...

Aminoacyl-Transfer RNA Maturation

Sylvain Blanquet, Yves Mechulam, Emmanuelle Schmitt and Lionel Vial

Some aminoacylated tRNAs are subject to specific maturation. These maturations can be necessary either to produce the correct aminoacylated species for the ribosome or to regenerate toxic or nonproductive tRNAs produced after errors of the translational machinery. This chapter will first...

Aminoacyl-tRNA Synthetase Structure and Evolution

Dieter Söll and Michael Ibba

The pairing of codons in mRNA with tRNA anticodons determines the order of amino acids in a protein. It is therefore imperative for accurate translation that tRNAs are only coupled to amino acids corresponding to the RNA anticodon. This is mostly, but not exclusively, achieved by the dir...

Aminoacyl-tRNA Synthetases and Disease

Michael Kron and Michael Härtlein

Doctor to Lady Macbeth: This disease is beyond my practice… I think, but dare not speak. Lady Macbeth: Hell is murky. - Act V, scene I. Macbeth, by William Shakespeare. Understanding the role of aminoacyl-tRNA synthetases (AARS) in human, animal or plant disease is a challenging work in p...

Aminoacyl-tRNA Synthetases As Anti- Infective Drug Targets

John Finn and Jianshi Tao

The increase in resistance to existing antibiotics has emerged as a major problem in healthcare. New antimicrobial agents with novel mechanisms of action need to be developed to address the urgent need for treating resistant infections. Aminoacyl-tRNA synthetases have been validated as potential...

Aminoglycosides and Cleavage of the Hairpin Ribozyme

David J. Earnshaw and Michael J. Gait

The hairpin ribozyme belongs to a class of small naturally occurring ribozymes which includes the hammerhead, the hepatitis delta virus and the Neurospora VS ribozyme that in each case generates identical cleavage products that contain 5'hydroxyl and 2',3'cyclic phosphate termini. How...

Antibiotics as Indicators of the Functional Components of the Ribosome

D. Fourmy, S. Yoshizawa and S. Douthwaite

The inhibitory action of many antibiotics is to block directly the synthesis of proteins on the bacterial ribosome. How these antibiotics interact with their targets on the bacerial ribosome has been the focus of considerable scrutiny over the last four decades. It was envisaged that elucidation of ...

Arginyl-tRNA Synthetase

Gilbert Eriani and Jean Cavarelli

Determination of the crystal structures of arginyl-tRNA synthetase, either in the free state or engaged in complexes with the other partners of the arginylation reaction, led to fundamental progress in understanding the sequence-structure-function relationship of this catalytic reaction. The structu...

Asparaginyl-tRNA Synthetase: Pathways and Evolutionary History of tRNA Asparaginylation

Daniel Kern, Herve Roy and Hubert Dominique Becker

Asparaginylation of tRNA presents the unusual character that it can be performed by two distinct pathways. A direct, and probably modern one, consisting in direct attachment of Asn on tRNAAsn by asparaginyl-tRNA synthetase (AsnRS), and an indirect, likely ancestral one, in which a mischarged As...

Aspartyl-tRNA Synthetases

Richard Giege and Bernard Rees

Aspartyl-tRNA synthetases (AspRSs) belong to subclass IIb of synthetases. The subunits of these dimeric proteins have a conserved modular architecture in the three kingdoms of life, comprising a C-terminal active site domain linked by a short hinge domain to an N-terminal anticodon-binding domai...

Behavior of the Nucleolus during Mitosis

Danièle Hernandez-Verdun

The nucleolus is the ribosome factory and also a multifunctional domain that plays an important role in nuclear organization and function. The nucleolus is assembled at the end of mitosis, is active during interphase, and dis-assembled in prophase. The nucleolar machineries of transcription and p...

Brain-Specific Nonmessenger RNAs

Jürgen Brosius, Alexander Hüttenhofer and Henri Tiege

RNAs that do not encode proteins, as do messenger RNAs, play much more prominent roles in the functioning of cells than we first anticipated–qualitatively and quantitatively. At least in Eukarya one has the impression that we have hardly left the RNA world. This RNA life is not only a remnant fro...

Catalysis of the tRNA Aminoacylation Reaction

Eric A. First

Aminoacyl-tRNA synthetases catalyze the attachment of amino acids to the 3’ end of tRNA in a two step reaction. In the first step, the amino acid is activated by ATP, forming the enzyme-bound aminoacyl-adenylate intermediate. In the second step of the reaction, the activated amino acid is tran...

Class I Lysyl-tRNA Synthetases

Alexandre Ambrogelly, Dieter Soll, Osamu Nureki, Shigeyuki Yokoyama and Michael Ibba

Lysyl-tRNA synthetases are unique amongst the aminoacyl-tRNA synthetases in that they are found as both class I and class II enzymes. Most bacteria and all eukaryotes contain a class II LysRS whereas most archaea and a few bacteria contain a less common class I LysRS. In bacteria the class I Ly...

Class II Lysyl-tRNA Synthetases

Sylvain Blanquet, Pierre Plateau and Silvia Onesti

The three-dimensional structure of lysyl-tRNA synthetase closely resembles that of the aspartyl- and asparaginyltRNA synthetases. Altogether, the three enzymes constitute subclass IIb within the family of aminoacyl-tRNA synthetases. One specific feature of this subclass is the recognition of the...

Cleavage of RNA by Fe(II)-Bleomycin

Pradip Mascharak and Alexander Hüttenhofer

Clinical success of the bleomycin family of glycopeptide antibiotics in combination chemotherapy against several types of cancer1-3 is believed to be related to their ability to bind to cellular DNA and inflict strand breaks in the presence of metal ions and dioxygen.4,5

Complex Alternative Splicing

Jung Woo Park and Brenton R. Graveley

Alternative splicing is a powerful means of controlling gene expression and increasing protein diversity. Most genes express a limited number of mRNA isoforms, but there are several examples of genes that use alternative splicing to generate hundreds, thousands and even tens of thousands of isoforms...

Computational Gene-Finding for Noncoding RNAs

Peter Schattner

Computer gene-finding programs have been quite successful at locating protein-coding genes in both prokaryotic and eukaryotic genomes. However these programs—which use genomic features such as long open-reading-frames and codon signatures—are not designed to identify non-coding RNA (n...

Conformational Dynamics within the Ribosome

J. Stephen Lodmell and Scott P. Hennelly

The ribosome is a dynamic particle that undergoes an iterative series of conformational changes during translation. Individual structural changes in the ribosome in response to tRNA or mRNA binding, initiation or elongation factor binding, buffer conditions, and antibiotic effects have b...


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