Multiple determinants of eukaryotic mRNA stability.
Regulated changes in mRNA stability play an important role in modulating the level of expression of many eukaryotic genes. In several systems, specific sequence determinants that dictate mRNA instability have been identified. Thus, the presence of instability determinants, and not the absence of sequences that dictate stability, appears to be required for regulated mRNA degradation. These instability determinants presumably interact with specific nucleases or other trans-acting factors that regulate the accessibility of the domain to nucleases. Although each RNA destabilization pathway has unique features, in many cases RNA degradation requires ongoing protein synthesis. In some of the systems discussed, the mRNAs are degraded co-translationally, perhaps by a ribosome-associated ribonuclease. For other messages, the mechanistic reasons for the dependence of mRNA degradation on ongoing protein synthesis are still unknown.
Cleveland
D W
DW
Department of Biological Chemistry, Johns Hopkins University, School of Medicine, Baltimore, MD 21205.
Yen
T J
TJ
D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D005057:Eukaryotic Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D016259:Genes, myc; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006657:Histones / Q000235:genetics; D006728:Hormones / Q000502:physiology; D007501:Iron / Q000494:pharmacology; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D011519:Proto-Oncogenes; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000378:metabolism; D011990:Receptors, Transferrin / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D012260:Ribonucleases / Q000378:metabolism; D014404:Tubulin / Q000235:genetics
D006657:Histones; D006728:Hormones; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011990:Receptors, Transferrin; D014404:Tubulin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007501:Iron; D012260:Ribonucleases