In eukaryotic cells, mRNAs are transcribed as pre-mRNA and processed into mature mRNA in the nucleus, then transported through nuclear pore complexes to the cytoplasm. In some cases, mRNAs are transported to specific areas of the cytoplasm before being translated by ribosomes.
Complex macromolecular machines, such as spliceosomes and the cleavage/ polyadenylation apparatus, control each of these fundamental processes. These macromolecular assemblages comprise scores of proteins, and in many cases RNAs. The complexity of these control-assemblages ensures accuracy in locating promoters and splice sites in the long length of DNA and RNA sequences. Further, the macromolecular machines provide various avenues for regulating synthesis of a polypeptide chain.
Regulation of mRNA stability is central to the post-transcriptional modulation of gene expression. Stability of mRNA varies considerably between mRNAs and can be modulated by extracellular stimuli. Tight control of mRNA stability permits rapid changes mRNA levels, providing a mechanism for prompt termination of protein production. The rate of mRNA decay is determined by cis-acting sequences within the mRNA, which are recognized by trans-acting factors. The best-characterized cis-acting sequences responsible for mRNA decay in mammalian cells are the AU-rich elements, AREs present within the 3'-UTRs of short-lived mRNAs. These AREs are involved in deadenylation and subsequent degradation of mRNAs, and they have also been observed to stimulate 5'-decapping.
Dysregulation of mRNA stability has been associated with different chronic inflammatory diseases, -thalassemia, cancer, and Alzheimer's disease.A number of ARE binding proteins (ARE-bps) have been identified, which interact with AU- and U-rich regions. These include the ELAV protein family members (most important HuR), the ARE/poly-(U)-binding/degradation factor 1 (AUF-1, also named hnRNP D), the heteronuclear ribonucleoprotein A1 (hnRNP A1), the KH-type splicing regulatory protein (KSRP), tristetraprolin (TTP), the T cell-restricted intracellular antigen (TIA)-1 and the TIA-related protein (TIAR). The KH-type splicing regulatory protein, KSRP has been described as being essential for exosome-mediated degradation of ARE-containing mRNAs.
Full Text Research Article on KSRP-mediated reduction of iNOS expression.animation - life cycle of an mRNA : animation ~ alternative splicing : NCBI Molecular Cell Biology - Contents : Google mRNA : Classes of RNA Polymerases : Mechanism of RNA Polymerases : Processes of Transcription : Post-transcriptional Processing of RNAs : RNA Splicing : Clinical Significance of Alternative and Aberrant Splicing
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