SnoRNA

Although we will stick to the IL-6 gene, it should be mentioned at the side that two other RNA polymerases exist in mammalian cells responsible for the synthesis of RNA molecules, which are not translated into proteins ribosomal (rRNA), transfer (tRNA), small nuclear (snRNA), small nucleolar (snoRNA), and some of the recently discovered microRNAs and piRNAs. These RNA molecules act in the process of translation and mRNA turnover. Micro and piRNAs are probably extremely important in the definition of stem cells and of differentiation programs. Some of them are synthesized by RNA polymerase II. 

FIGURE 26-22 Processing of pre-rRNA transcripts in vertebrates. In step (T), the 45S precursor is methylated at more than 100 of its 14,000 nucleotides, mostly on the 2 -OH groups of ribose units retained in the final products. (5) A series of enzymatic cleavages produces the 18S, 5.8S, and 28S rRNAs. The cleavage reactions require RNAs found in the nucleolus, called small nucleolar RNAs (snoRNAs), within protein complexes reminiscent of spliceosomes. The 5S rRNA is produced separately. 

Polymerase II Transcription of most genes to give precursors to mRNA and most small nuclear RNAs (snRNAs and small nucleolar RNAs (snoRNAs)... 

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. 

The most abundant protein in the fibrillar regions of the nucleus, where the early stages of pre-rRNA processing occur, is fibrillarin.541,548,549 Many of the snoRNAs are closely associated with this protein. Fibrillarin is also well known as an autoantigen, which can induce formation of destructive antibodies that cause scleroderma (Chapter 31, Section F). 

Lafantavine, D.L.J. and Tollervey, D. (1998) Birth of the snoRNPs the evolution of the modification guide snoRNAs. Trends Biochem. Sci. 23, 383-386. 

A snoRNA HBII-52 is located in the defective region of PWS. HBH-52 binds to an ESS in exon Vb of HTR2C encoding the serotonin receptor 2C, and its disruption in PWS causes aberrant splicing of HTR2C and potentially accounts for dysfunctional serotonergic system in PWS (Kishore and Stamm, 2006). 

Kimura T, Nakamori M, Lueck JD, PouUquin P, Aoike F et al (2005) Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic/endoplasmrc reticulum Ca2+-ATPase in myotonic dystrophy type 1. Hum Mol Genet 14 2189-2200 Kishore S, Stamm S (2006) The snoRNA HBll-52 regulates alternative splicing of the serotonin receptor 2C. Science 311 230-232... 

RNA, small nuclear (snRNA) and small nucleolar (snoRNA), Chemistry of... 

Other hnRNA (heterogeneous nuclear, such as snoRNA - small nucleolar). 

The cleavage of the precursor into three separate rRNAs is actually the final step in its processing. First, the nucleotides of the pre-rRNA sequences destined for the ribosome undergo extensive modification, on both ribose and base components, directed by many small nucleola.r ribonucleo-proteins (snoRNPs), each of which consists of one snoRNA and several proteins. The pre-rRNA is assembled with ribosomal proteins, as guided by... 

Different types of substitution/conversion-editing have been described. The best characterised involves cytidine deamination to uridine in the editing of transcripts for apolipoprotein B, and adenosine deamination to inosine in the editing of the transcripts encoding the glutamate receptor subunits. More than 90 different types of base modifications have been described. Moreover, methylations and substitutions of the ribose and phosphate moieties have also been identified. Recently, the 2 -0-ribose methylation has been the focus of much attention since the discovery that the snoRNA guides the methylation in a frans-acting fashion. 

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