Department of Molecular Neuro-Oncology, The Rockefeller University, 1230 York Ave., New York, NY 10065, USA.
Curr Opin Genet Dev. 2011 Aug;21(4):465-73. doi: 10.1016/j.gde.2011.05.002. Epub 2011 Jul 19.
Recent data suggest that the levels of many synaptic proteins may be tightly controlled by the opposing processes of new translation and protein turnover in neurons. Alterations in this balance or in the levels of such dosage-sensitive proteins that result in altered stoichiometry of protein complexes at developing and remodeling synapses may underlie several human cognitive diseases including Fragile X Syndrome, autism spectrum disorders, Angelman syndrome and non-syndromic mental retardation. While a significant amount is known about the transduction of membrane signals to the translational apparatus through kinase cascades acting on general translation factors, much less is understood about how such signals may influence the activity of mRNA-specific regulators, their mechanisms of action and the specific sets of mRNAs they regulate. New approaches to the unbiased in vivo identification of maps of binding sites for these proteins on mRNA is expected to greatly increase our understanding of this crucial level of regulation in neuronal development and function.
最近的数据表明，许多突触蛋白的水平可能受到神经元中新翻译和蛋白质周转的相反过程的严格控制。这种平衡的改变，或者导致蛋白质复合物在发育和重塑突触时的化学计量发生改变的这种剂量敏感蛋白的水平的改变，可能是几种人类认知疾病的基础，包括脆性 X 综合征、自闭症谱系障碍、天使综合征和非综合征性智力迟钝。虽然已经了解了通过作用于一般翻译因子的激酶级联将膜信号转导到翻译装置的大量信息，但对于这些信号如何影响 mRNA 特异性调节剂的活性、它们的作用机制以及它们调节的特定 mRNA 集，了解甚少。新的方法可以在体内无偏地鉴定这些蛋白质在 mRNA 上的结合位点图谱，这有望大大提高我们对神经元发育和功能中这种关键调节水平的理解。
