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INTRODUCTION

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OBJECTIVES

After studying this chapter, you should be able to:

  • Describe the molecules involved and the mechanism of RNA synthesis.

  • Explain how eukaryotic DNA-dependent RNA polymerases, in collaboration with an array of specific accessory factors, can differentially transcribe genomic DNA to produce specific mRNA precursor molecules.

  • Describe the structure of eukaryotic mRNA precursors, which are highly modified internally and at both termini.

  • Appreciate the fact that the majority of mammalian mRNA-encoding genes are interrupted by multiple non-protein coding sequences termed introns, which are interspersed between protein coding regions termed exons.

  • Explain that since intron RNA does not encode protein, the intronic RNA must be specifically and accurately removed in order to generate functional mRNAs from the mRNA precursor molecules in a series of precise molecular events termed RNA splicing.

  • Explain the steps and molecules that catalyze mRNA splicing, a process that converts the end-modified precursor molecules into mRNAs that are functional for translation.

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BIOMEDICAL IMPORTANCE

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The synthesis of an RNA molecule from DNA is a complex process involving one of the group of DNA-dependent RNA polymerase enzymes and a number of associated proteins. The general steps required to synthesize the primary transcript are initiation, elongation, and termination. Most is known about initiation. A number of DNA regions (generally located upstream from the initiation site) and protein factors that bind to these sequences to regulate the initiation of transcription have been identified. Certain RNAs—mRNAs in particular—have very different life spans in a cell. The RNA molecules synthesized in mammalian cells are made as precursor molecules that have to be processed into mature, active RNA. It is important to understand the basic principles of messenger RNA (mRNA) synthesis and metabolism, for modulation of this process results in altered rates of protein synthesis and thus a variety of both metabolic and phenotypic changes. This is how all organisms adapt to changes of environment. It is also how differentiated cell structures and functions are established and maintained. Errors or changes in synthesis, processing, splicing, stability, or function of mRNA transcripts are a cause of disease.

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RNA EXISTS IN TWO MAJOR CLASSES

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All eukaryotic cells have two major classes of RNA (Table 36–1), the protein coding RNAs, or messenger RNAs (mRNAs), and two forms of abundant non-protein coding RNAs delineated on the basis of size: the large ribosomal RNAs (rRNA) and long noncoding RNAs (lncRNAs) and small noncoding RNAs transfer RNAs (tRNA), the small nuclear RNAs (snRNAs) and the micro and silencing RNAs (miRNAs and siRNAs). The mRNAs, rRNAs and tRNAs are directly involved in protein synthesis while the other RNAs are participate in either mRNA splicing (SnRNAs) or modulation of gene expression by altering mRNA function (mi/SiRNAs) and/or expression (lncRNAs). These RNA differ in their diversity, stability, and abundance in cells.

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