6533b85dfe1ef96bd12bf23f

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Kinetic models for nucleocytoplasmic transport of messenger RNA

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Abstract Much is known about the mechanism by which mRNAs cross the nuclear envelope (the translocation stage of nucleocytoplasmic transport), but far less is known about the preceding (intranuclear migration/release) and succeeding (cytoplasmic binding) stages. Therefore, existing information suffices for articulating detailed kinetic models of translocation, but not models for the overall mRNA transport process. In this paper, we show that simple kinetic models of translocation can (i) accommodate date about nucleocytoplasmic distributions of endogenous transcripts; (ii) predict the overall effects on these distributions of effectors such as insulin and epidermal growth factor; (iii) throw some light on the machanism(s) of action of the HIV-1 protein Rev and produce experimentally testable predictions about this mechanism; and (iv) account for the action of influenza virus NSI protein. However, the simplest forms of translocation models apparently fail to account for some properties of viral regulators such as HIV Rev and adenovirus E1B-E4 complex. To elucidate these topics, less narrowly focused models of mRNA transport are required, describing intranuclear binding/release as well as translocation. On the basis of our examination of translocation models, we suggest some criteria that the requisite broadly based models must satisfy.