Early nonsense: mRNA decay solves a translational problem
 Nature Reviews Molecular Cell Biology 7, No 6, 415-425 (June 2006) | doi:10.1038/nrm1942 | |
 Рис.1. | The mRNA 'life cycle' in the cytoplasm.  Рис.2. | Model for the regulation of CPA1 upstream open reading frame translation and mRNA degradation.  Рис.3. | Stabilization of nonsense-containing mRNA by tethered Pab1.  Рис.4. | Proposed mechanistic differences between normal and premature translation termination in yeast. Box 1 | Translation termination in eukaryotes Box 2 | Regulators of NMD Box 3 | Toeprinting analysis | Экспрессия генов очень аккуратна и редко генерирует дефектные белки. Специальные механизмы гарантируют эту точность, включая сперциализированные пути надзора, которые избавляют клетки от мРНК, которые подверглись неполному процессингу или которые лишены полной открытой рамки считывания. Один из таких механизмов, nonsense-обусловленный распад мРНК, запускается, когда рибосомы наталиваются на преждевременного окончания транлсляции — или nonsense — кодон. Новые доказательства указывают на то, что специализированные факторы, которые рекрутируются в ходе этого процесса не только способстуют деградации мРНК, но и также необходимы для устранения плохо диссоциируемого комплекса терминации.
Сoncluding remarks
An important corollary of the preceding discussion is that current concepts of the mechanism of translation termination are vastly oversimplified. Prevalent models ascribe most of the crucial functions in termination to two release factors, even though the comparably complicated process of initiation is already known to involve as many as 100 factors. Analyses of nonsense-mediated mRNA decay (NMD) discussed here, as well as other studies of the modulation of eRF activity7,125-127, indicate considerable regulation of the termination process and the probable involvement of numerous additional factors. The complexities of termination remain to be unravelled, but our understanding of NMD has already taught us that there can be at least two modes of termination, that the activity of the release factors alone cannot account for all termination functions, and that the proteins that interact with the release factors and the proteins that bind to them can have important roles in post-transcriptional regulation. In addition, the 3'-UTR along with Pab1 might orchestrate the termination of translation in much the same way that the 5'-UTR and the translation initiation protein eIF4G function in initiation. |