Structural RNA

In mid-1997 an international conference took place in Santa Cruz, USA, in which, for the first time, the exclusive topic was structural aspects of RNA molecules. A report covering this meeting contains an impressive graphic which shows the RNA structures, RNA/DNA complexes, and RNA/protein complexes contained in the brookhaven database as a function of the year of their publication [29]. Between 1988 and 1993 there were just 20. However, in 1996 alone no less than 41 structures appeared. These new dimensions were headed by the crystal structural elucidation of the first larger RNA molecule since the first crystal structure of tRNA in 1973 [30], the 48 nucleotide long hammerhead ribo-zyme (HHR) [31-33]. This landmark achievement was followed by a crystal structure analysis of the P4-P6-domain of a group I intron [34-36] and, more recently, a crystal structure of the hepatitis delta virus ribozyme [37]. 

In contrast to DNA, which is quite generally found in a double-stranded structure, RNA is generally, but not always, found in nature as a single-stranded molecule. There are, as always, exceptions, one of which we note below. Double-stranded RNAs as well as hybrid DNA RNA double-stranded molecules are found. 

Trace metals Zinc Red meats, shellfish, wholegrain cereals Involved in many metabolic reactions stabilisation of structure RNA, DNA and ribosomes Binding of some transcription factors to DNA Stabilisation of insulin complex in storage granules... 

Fig. 10.6 Concept of multitarget affinity specificity screening (MASS). Macromolecular targets (typically structured RNA constructs or proteins) in nondenaturing buffers are mixed in solution with a collection of potential ligands derived from natural product fractions, combinatorial libraries, or other diverse compound collections. The...

R. H., Draper, D. E. Magnesium ion, fhiostrepton, and ribosomal protein Lll all induce folding of the same rRNA tertiary structure. RNA 1999. 

SAR by MS a ligand based technique for drug lead discovery against structured RNA targets. J Med Chem 2002, 45, 3816-3819. 

Zuker, M. and Jacobson, A. B. (1998). Using rehabihty information to annotate RNA secondary structures. RNA 4, 669-679. 

The sequence of the bases contains coded information for the synthesis of proteins. These sequences are transcribed into an RNA copy of the sequence messenger RNA (mRNA). The mRNA is translated in the cytoplasm. The DNA also encodes structural RNAs, with functions in transcription of the DNA, processing of the transcripts and translation of the transcripts. The genetic code shown in Table 8.2.1 is simple, but efficient. At each nucleotide position, there are only four possibilities A,... 

Molecular evolution demands inherent self-reproductivity. RNA seems to fulfill this function best of all known macromolecules. On account of its complex structure RNA must first have appeared in nature long after proteins or protein-like structures. A protein can by chance fulfill a particular function, but this fulfilment is determined by purely structural and not at all by functional criteria. Adaptation to a particular function, however, demands an inherent mechanism of self-reproduction. The only logically justifiable way of exploiting the immense functional capacity of the proteins in evolution lies in an intermarriage between these two classes of macromolecules, that is, in the translation into protein of the information stored in the self-reproductive RNA structures. 

Davis, J.H. and Szostak, J.W. (2002) Isolation of high-affinity GTP aptamers from partially structured RNA libraries, Proc. Natl. Acad. Sci. USA 99, 11616-11621. 

The gene encoding the smallest structural RNA component of the nuclear ribosome is the 5S rRNA gene. This gene is not co-located with the remaining nuclear rRNA genes. Neither sequence nor chromosomal location of the 5S gene is known for any neodermatan and it will not be discussed further here. 

This chapter will focus on the use of native PAGE to investigate folding of the Tetrahymena group I ribozyme. However, these protocols are easily adapted to other ribozymes and structured RNAs (e.g., Adilakshmi et ah, 2005 Lafontaine et ah, 2002 Pinard et ah, 2001 Severcan et ah, 2009). Detailed discussions of gel mobility shift methods for measuring protein—... 

Structure RNA Models to Three-Dimensional Shape Models 243... 

Low-Resolution Atomic Scale Models of RNA [X Fitting Secondary Structure RNA Models to Three-Dimensional Shape Models... 

Like other macromolecules, RNA is dynamic. The process of folding into a structured RNA involves dynamic rearrangement of RNA helices, and many RNAs function via a series of conformational transitions. Thus, measurement of the dynamics of individual helices will be required to fully understand RNA folding and function. Additionally, dynamic information can also be used to provide information about local structural features. 

Structured RNAs that are significantly smaller than the Tetrahymena ribozyme can be studied in the same way as a model oligonucleotide... 

One of the problems with DNA is that it is essentially a linear code that stores information. The functional groups (nucleotides) only interact with each other and, while this can lead to the elegant double helix, it limits the ability of DNA to form different secondary and extensive tertiary structures. RNA is rather more amenable to forming other structural motifs, hence the RNA World theory of molecular evolution, but it appears that only proteins with their varied side chains are able to adopt truly complex structures. 

There are several large classes of DNA sequences which are not translated, including those for structural RNAs [ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs)], pseudogenes, and repetitive DNAs [e.g., short and long interspersed repeated sequences (SINES and LINES)]. Ribosomal... 

Stems and loops likely to change than the latter Selective weighting of double-stranded (stem) versus single- 1 stranded (loop) regions of structural RNAs (tRNA and... 

No. Eukaryotic RNA polymerases have been isolated from many tissues, and in all cases, three distinct enzymes have been found in the nucleus. All contain a number of polypeptide subunits and are complex in structure, RNA polymerase I is known to be involved specifically in the transcription of rRNA genes. RNA polymerase II gives rise to transcripts that are subsequently processed to yield mRNA. RNA polymerase 111 is responsible for the transcription of the tRNA genes and a small ribosomal RNA gene that yields a species called 55 RNA. The three polymerases are distinguishable from one another by their differential sensitivity to the drug a-amanitin (the toxic principle of the mushroom Amanita phalloides), which does not affect bacterial RNA polymerase. RNA polymerase... 

These results indicate that RNA in a DNA-RNA hybrid is protected from cleavage Ly Eu(L1)3+ under conditions where nearly all other sites in tRNAphe are cleaved. We cannot rule out poorer binding of the metal complex to the hybrid than to RNA alone. There is ample precedence for binding of Eu(III) ions to double-stranded nucleic acids (34). Eu(III) is also known to bind well to pockets in highly structured RNAs such as tRNA (31). It is not known how the europium complex will bind to these different structures. 

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