Although most mRNAs in mammalian cells are very stable (half-lives measured in hours), some turn over very rapidly (half-lives of 10-30 minutes). In certain instances, mRNA stability is subject to regulation. This has important implications since there is usually a direct relationship between mRNA amount and the translation of that mRNA into its cognate protein. Changes in the stability of a specific mRNA can therefore have major effects on biologic processes.

Messenger RNAs exist in the cytoplasm as ribonucleoprotein particles (RNPs). Some of these proteins protect the mRNA from digestion by nucleases, while others may under certain conditions promote nuclease attack. It is thought that mRNAs are stabilized or destabilized by the interaction of proteins with these various structures or sequences. Certain effectors, such as hormones, may regulate mRNA stability by increasing or decreasing the amount of these mRNA-binding proteins.

It is known that the ends of mRNA molecules are involved in mRNA stability (Figure 1). The 5′–cap structure in eukaryotic mRNA prevents attack by 5′ exonucleases, and the poly(A) tail minimizes the action of 3′ exonucleases. In mRNA molecules with those structures, it is presumed that a single endonucleolytic cut allows exonucleases to attack and digest the entire molecule. Other structures (sequences) in the 5′–untranslated region (5′ UTR), the coding region, and the 3′ UTR are thought to promote or prevent this initial endonucleolytic action (see Figure 1).

Fig1. Structure of a typical eukaryotic mRNA showing elements that are involved in regulating mRNA stability. The typical eukaryotic mRNA has a 5′–noncoding sequence (NCS), or untranslated exonic region (5′ UTR), a coding region, and a 3′–exonic untranslated NCS region (3′ UTR). Essentially all mRNAs are capped at the 5′ end, and most have a 100 to 200 nt polyadenylate sequence at their 3′ end. The 5′ cap and 3′ poly(A) tail protect the mRNA against exonuclease attack and are bound by specific proteins that interact to facilitate translation. Stem-loop structures in the 5′ and 3′ NCS, and the AU-rich region in the 3′ NCS represent the binding sites for specific proteins that modulate mRNA stability.

Thus, it is clear that a number of mechanisms are used to regulate mRNA stability and hence function—just as several mechanisms are used to regulate the synthesis of mRNA, and as detailed in Chapter 37, mRNA translation. Coordinate regulation of these processes confers on the cell remarkable adaptability.

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مواضيع ذات صلة

Eukaryotic Genes Can Be Amplified or Rearranged During Development or in Response to Drugs

The DNA Binding & Transactivation Domains of Most Regulatory Proteins are Separate DNA

Several Structural Motifs Compose the DNA-Binding Domains of Regulatory Transcription Factor Proteins

Reporter Genes Are Used to Define Enhancers & Other Regulatory Elements That Modulate Gene Expression

Certain DNA Elements Enhance or Repress Transcription of Eukaryotic Genes

Epigenetic Mechanisms Contribute Importantly to the Control of Gene Transcription

The Chromatin Template Contributes Importantly to Eukaryotic Gene Transcription Control

The Genetic Switch of Bacteriophage Lambda (λ) Provides Another Paradigm for Understanding the Role of Conditional Regulatory Protein-DNA Interactions in Transcriptional Control in Eukaryotic Cells

Analysis of Lactose Metabolism in E. coli Led to the Discovery of the Basic Principles of Gene Transcription

Biologic Systems Exhibit Three Types of Temporal Responses to a Regulatory Signal

Regulated Expression of Genes is Required for Development, Differentiation, & Adaptation

Posttranslational Processing Affects the Activity of many Proteins