Small RNAs

HammerheadRtbozyme. A small RNA molecule that catalyzes cleavage of the phosphodiester backbone of RNA is known as the hammerhead ribozyme. This ribozyme occurs namrally in certain vimses where it facihtates a site-specific self-cleavage at the phosphate and generates a 2 3 -cychc phosphate and a 5 -hydroxyl terminus. The reaction requires a divalent metal ion, such as or, as a cofactor. Whereas the... 

In most four-helix bundle structures, including those shown in Figure 3.7, the a helices are packed against each other according to the "ridges in grooves" model discussed later in this chapter. However, there are also examples where coiled-coil dimers packed by the "knobs in holes" model participate in four-helix bundle structures. A particularly simple illustrative example is the Rop protein, a small RNA-binding protein that is encoded by certain plasmids and is involved in plasmid replication. The monomeric sub unit of Rop is a polypeptide chain of 63 amino acids built up from two... 

Capsids can also be formed in the absence of RNA as well as in the presence of small RNA molecules comprising the 19 nucleotides of the... 

Table 1. Picornavirus Characteristics (Very Small RNA Viruses)...

Ribozymes that are small RNA molecules with endoribonuclease activity and exhibit catalytic sequence-specific cleavage of the target. 

Rana TM (2007) Illuminating the silence understanding the structure and function of small RNAs, Nat Rev Mol Cell Biol 8 23-36... 

There are three distinct nuclear DNA-dependent RNA polymerases in mammals RNA polymerases I, II, and III. These enzymes control the transcriptional function—the transcription of rRNA, mRNA, and small RNA (tRNA/5S rRNA, snRNA) genes, respectively. 

DNA polymerase I is a nonessential enzyme, since viable E. coli mutants lack it (pol A). This conclusion is complicated, however, since the enzyme catalyzes three separate chemical reactions. It polymerizes deoxyribonucleoside triphosphates, and it has two exonucleolytic activities, a 3 to 5 activity and a 5 to 3 activity. The pol A - mutants lack only the polymerization activity. Other mutants lacking both the polymerase and the 5 to 3 exonuclease activity are lethal. Thus the exonuclease function is the more important one. This fits with the role of this enzyme in removing damaged DNA segments (DNA repair) and in removing covalently attached RNA from DNA chains. We will later see that small RNAs serve as primers of DNA synthesis. 

Masse E. and Gottesman, S. (2002). A small RNA regulates the expression of genes involved in iron metabolism in Escherichia coli. Proc. Natl. Acad. Sci., 99, 4620 1625... 

Couzin, J. (2002). Small RNAs make a big splash. Science, 298, 2296-2297... 

Ribonucleic acid (RNA) Molecules including messenger RNA, transfer RNA, ribosomal RNA, or small RNA. RNA serves as a template for protein synthesis and other biochemical processes of the cell. The structure of RNA is similar to that of DNA except for the base thymidine being replaced by uracil. 

Steitz JA, Tycowski KT. Small RNA chaperones from ribosome biogenesis. 

Zamore PD, Haley B (2005) Ribo-gnome the big world of small RNAs. Science 309 1519-1524... 

Grewal SI, Rice JC (2004) Regulation of heterochromatin by histone methylation and small RNAs. Curr Opin Cell Biol 16 230-238... 

Final question how big are the nucleic acids How many nucleotide units do we typically find in DNA or RNA The answer is enormously variable. There are small RNA molecules that contain 25 or fewer nucleotides there are also RNA molecules that contain thousands of nucleotides. But for really, really big molecules, we turn to DNA, which may have tens of thousands of nucleotides linked together Specific examples follow below but we need some additional insights first. 

The counterpart of DNA polymerases in replication is RNA polymerases in transcription. Just as there are several DNA polymerases in vertebrate cells, so there are several RNA polymerases. To be precise, there are three of them. The different RNA polymerases are associated with three of the classes of RNA molecules found in vertebrate cells. Specifically, RNA polymerase I is responsible for the synthesis of the precursors of most rRNAs. RNA polymerase II plays the same role for the precursors of mRNA. Finally, RNA polymerase III is responsible for the synthesis of the precursors to the tRNAs as well as a few other small RNA molecules. Note here that I have specifically referred to precursors of these classes of RNA molecules. The initial products of the action of the RNA polymerases undergo further metabolism to yield the mature, functional products. 

This definition expands our earlier thoughts in two ways. First, we have included specification of RNA molecules as well as proteins. As noted above, many RNA molecules serve a role as message carrier from DNA to the protein-synthesizing machinery (mRNA) and are translated into protein structures. Other RNA molecules serve other functions as components of the ribosome, rRNA, or as an interface between mRNA and amino acids in protein synthesis, tRNA. Finally, we have the very small RNA molecules known as siRNA. These species of RNA are not translated into proteins and this requires that the definition of a gene include the specification of their structure. 

RNA polymerase III catalyses the synthesis of small RNA molecules, such as the transfer RNAs (see below). 

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. 

The illustration opposite shows selected nucleic acid molecules. Fig. A shows various conformations of DNA, and Fig. B shows the spatial structures of two small RNA molecules. In both, the van der Waals models (see p. 6) are accompanied by ribbon diagrams that make the course of the chains clear. In all of the models, the polynucleotide backbone of the molecule is shown in a darker color, while the bases are lighter. 

Khan AA, Betel D, Miller ML et al (2009) Transfection of small RNAs globally perturbs gene regulation by endogenous microRNAs. Nat Biotechnol 27 549-555... 

Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75 843-854... 

Joyce CE, Zhou X, Xia J et al (2011) Deep sequencing of small RNAs from human skin reveals major alterations in the psoriasis miR-NAome. Hum Mol Genet 20 4025-4040... 

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