RRNA, mammalian cells

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. 

Nuclear rRNA precursors and cytoplasmic rRNA formed by RNA polymerase I account for some 70+% of mammalian cell RNA and 35-40% of total RNA synthesis. The products of RNA polymerase II, hnRNA and mRNA, comprise some 10% of the total RNA and 55-60% of total synthesis. The hnRNA and mRNA transcripts are unstable and have half-lives in higher eukaryotes of about 24 h, compared with an average half-life in bacteria of 90 s. Pre-tRNAs, synthesized along with 5 S rRNA by RNA polymerase III, are relatively stable, with an average half-life of 4-6 days. 

All three types of cellular RNA—mRNA, tRNA, and rRNA—are synthesized in E. coli by the same RNA polymerase according to instructions given by a DNA template. In mammalian cells, there is a division of labor among several different kinds of RNA polymerases. We shall return to these RNA polymerases in Chapter 28. 

Approximately 80 percent of the total RNA in rapidly growing mammalian cells (e.g., cultured HeLa cells) is rRNA, and 15 percent is tRNA protein-coding mRNA thus constitutes only a small portion of the total RNA. The primary transcripts produced from most rRNA genes and from tRNA genes, like pre-mRNAs, are extensively processed to yield the mature, functional forms of these RNAs. 

A typical mammalian cell contains 10-30 pg of total RNA. The majority of RNA molecules are tRNAs and rRNAs, which have a relatively long half-life. mRNA accounts for only 1-5% of the total cellular RNA. Some mRNA species have a half-life of minutes whereas others can have a half-life of many days. Some mRNAs comprise as much as 3% of the mRNA pool whereas others account less than 0.01%. Approximately 350000 00000 mRNA molecules are present in each single mammalian cell, made up of approximately 12000 different transcripts with an average length of approximately 2 kb (Tables 3.7, 3.8). 

The synthesis of stable RNA, particularly rRNA, is highly correlated with cellular growth rates and with changes in growth rates. The mechanism for controlling rRNA synthesis has been most studied in bacteria and mammalian cells although the correlation with growth has been demonstrated in lower eukaryotes as well. 

Especially at high concentrations. Cm may display toxic side effects on eukaryotic cells v>-threo-Cm (but not L-Cm) specifically inhibits the synthesis of mitochondrial proteins such as cytochrome-c oxidase (51) and induces mutations on the 16S rRNA in mitochondria (52). Cells that harbor CAT vectors show resistance to Cm toxicity. The pharmacological fate of Cm in mammalian cells primarily involves the inactivation mediated by glucuronyltransferase. 

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