Lessons (not) learned from mistakes about translation.
Some popular ideas about translational regulation in eukaryotes have been recognized recently as mistakes. One example is the rejection of a long-standing idea about involvement of S6 kinase in translation of ribosomal proteins. Unfortunately, new proposals about how S6 kinase might regulate translation are based on evidence that is no better than the old. Recent findings have also forced rejection of some popular ideas about the function of sequences at the 3' end of viral mRNAs and rejection of some ideas about internal ribosome entry sequences (IRESs). One long-held belief was that tissue-specific translation via an IRES underlies the neurotropism of poliovirus and the attenuation of Sabin vaccine strains. Older experiments that appeared to support this belief and recent experiments that refute it are discussed. The hypothesis that dyskeratosis congenita is caused by a defect in IRES-mediated translation is probably another mistaken idea. The supporting evidence, such as it is, comes from a mouse model of the disease and is contradicted by studies carried out with cells from affected patients. The growing use of IRESs as tools to study other questions about translation is discussed and lamented. The inefficient function of IRESs (if they are IRESs) promotes misunderstandings. I explain again why it is not valid to invoke a special mechanism of initiation based on the finding that edeine (at very low concentrations) does not inhibit the translation of a putative IRES from cricket paralysis virus. I explain why new assays, devised to rule out splicing in tests with dicistronic vectors, are not valid and why experiments with IRESs are not a good way to investigate the mechanism whereby microRNAs inhibit translation.
Kozak
Marilyn
M
Department of Biochemistry, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA. kozakma@umdnj.edu
D000818:Animals; D019871:Dyskeratosis Congenita / Q000209:etiology; D004486:Edeine / Q000494:pharmacology; D005057:Eukaryotic Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D008954:Models, Biological; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010442:Peptide Chain Initiation, Translational; D017955:Poliovirus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D011055:Poliovirus Vaccine, Oral; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D014779:Virus Replication
D035683:MicroRNAs; D019384:Nucleic Acid Synthesis Inhibitors; D011055:Poliovirus Vaccine, Oral; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D004486:Edeine; D019893:Ribosomal Protein S6 Kinases