RRNA loops

Rdblovd, K., Spackova, N., Stefl, R., Csaszar, K., Kofea, J., Leontis, N. B., Sponer, J. (2003). Non-Watson-Crick base pairing and hydration in RNA motifs Molecular dynamics of 5S rRNA Loop E. Biophysical Journal, 84, 3564. 

The small subunit 16S rRNA also contains regions that appear to be involved in translational accuracy. In particular, substitutions at nucleotides in the so-called 530 loop lead to changes in the error rate of protein synthesis. This rRNA loop is known to be spatially near the proteins S4, S5, and SI2, and effects of nucleotide changes in the 530 loop parallel those observed for the proteins. Thus, the rRNA and proteins in this part of the small subunit together act as a proofreading domain. Substitutions at some of these nucleotides increase the rate of missense or frameshift errors, while others are detrimental because they prevent binding of the EF-Tu GTP AA-tRNA ternary complex. Still other mutations actually increase the accuracy of translation, in that they make the ribosomes resistant to error-inducing antibiotics. 

To date, RNA calculations have been performed on a variety of systems of different topologies including helical duplexes, hairpin loops, and single strands from tRNA, rRNA, and ribozymes. In a simulation of an RNA tetraloop of the GRNA type, which is very common and known to be remarkably stable, it was found that without imposing any external infonnation the simulation found the right confonnation even when it started from the wrong one [72]. Studies have used Ewald summation methods to handle the... 

Ribosomal Protein Synthesis Inhibitors. Figure 5 Nucleotides at the binding sites of chloramphenicol, erythromycin and clindamycin at the peptidyl transferase center. The nucleotides that are within 4.4 A of the antibiotics chloramphenicol, erythromycin and clindamycin in 50S-antibiotic complexes are indicated with the letters C, E, and L, respectively, on the secondary structure of the peptidyl transferase loop region of 23S rRNA (the sequence shown is that of E. coll). The sites of drug resistance in one or more peptidyl transferase antibiotics due to base changes (solid circles) and lack of modification (solid square) are indicated. Nucleotides that display altered chemical reactivity in the presence of one or more peptidyl transferase antibiotics are boxed. 

Iordanov, M. S. et al. Ribotoxic stress response Activation of the stress-activated protein kinase JNK1 by inhibitors of the peptidyl transferase reaction and by sequence-specific RNA damage to the alpha-sarcin/ricin loop in the 28S rRNA. Mol. Cell. Biol. 17, 3373, 1997. 

In contrast to DNA, RNAs do not form extended double helices. In RNAs, the base pairs (see p.84) usually only extend over a few residues. For this reason, substructures often arise that have a finger shape or clover-leaf shape in two-dimensional representations. In these, the paired stem regions are linked by loops. Large RNAs such as ribosomal 16S-rRNA (center) contain numerous stem and loop regions of this type. These sections are again folded three-dimensionally—i.e., like proteins, RNAs have a tertiary structure (see p.86). However, tertiary structures are only known of small RNAs, mainly tRNAs. The diagrams in Fig. B and on p.86 show that the clover-leaf structure is not recognizable in a three-dimensional representation. 

Fig. 3 Secondary structure of the ribosomal rRNA of Saccharomyces cerevisiae. http //www.ma.icmb.utexas. edu (Cannone et al. 2002). The numbering of nucleotides is according to E. coli. Helices H) discussed in the text are highlighted and localization of yeast rdn mutations are indicated, a Secondary structure of the small subunit 18S rRNA. Helices discussed in the text are labeled in red. b Secondary structure of the 25 rRNA. Helices discussed in the text are labeled in blue. Helix 44 is part of the L7/L12 stalk hehx 95 contains the sarcin-ricin loop. For details, see text...

As is indicated in Fig. 28-15, transcription is thought to occur from the loops of DNA that form the nucleolar organizing region. The 100-kDa nucleolin, the major protein of the nucleolus, binds to the non-transcribed spacer sequences in the DNA.529-530 It also binds to the newly formed transcripts, as do various proteins that enter the nucleus from the cytoplasm.524531 More than 270 proteins, many of which participate in synthesis of ribosomes, have been detected in the nucleolus.5313 Some of these proteins, acting together with the snoRNAs discussed in the next section, catalyze hydrolytic cleavage of the pre-rRNA molecules. For completion of pre-ribosomal particles additional protein molecules enter the nucleolus and associate with the pre-rRNA particles, then diffuse out of the nucleus. 

Figure 28-17 (A) Electron micrograph of the 45S precursor of rRNA from HeLa cells after spreading from 80% formamide and 4 M urea. The molecule is shown in reverse contrast. (B) Tracing of molecule in (A) showing several regions of secondary structure as hairpin loops. The 28S and 18S rRNA regions are indicated. (C) 32S rRNA. (D) 28S rRNA. Notice that the same secondary structure can be seen in the 28S RNA as in its 32S and 45S precursors. From Wellauer and Dawid.527...

The sequences of all three pieces of RNA in the E. coli ribosomes are known as are those from many other species. These include eukaryotic mitochondrial, plas-tid, and cytosolic rRNA. From the sequences alone, it was clear that these long molecules could fold into a complex series of hairpin loops resembling those in tRNA. For example, the 16S rRNA of E. coli can fold as in Fig. 29-2A and eukaryotic 18S RNA in a similar way (Fig. 29-4).38/39/67 69 The actual secondary structures of 16S and 18S RNAs, within the folded molecules revealed by X-ray crystallography, are very similar to that shown in Fig. 29-2A. Ribosomal RNAs undergo many posttranscriptional alterations. Methylation of 2 -hydroxyls and of the nucleic acid bases as well as conversion to pseudouridines (pp. 1638-1641) predominate over 200 modifications, principally in functionally important locations that have been found in human rRNA.69a... 

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