Translational arrest

Several conditions must be kept in mind when studying SGs (1) SGs result from sudden translational arrest, which requires that the cells be actively translating at the application of the stress stimulus, (2) SGs are transient and may only be present for a limited time following the application of stress, and (3) different types of cells/cell lines respond differently to the same stress. These issues are described in detail. 

AS-ODN are designed to be complementary to the coding (sense) sequence of the mRNA in the cell. After hybridization to target sequences, translational arrest occurs via one of several putative mechanisms. The first mechanism is inhibition of transcription. Secondly, AS-ODN can prevent the synthesis of fully mature mRNA in the cytosol at the level of splicing. 

Translation arrest or nuclease digestion by exogenously applied antisense oligonucleotides or by antisense mRNA produced from DNA delivered by a plasmid. Heterogeneous nuclear RNA is hnRNA. 

Antisense DNA or RNA RNA2 Cytoplasm Translation arrest, RNase H activation, inhibition of splicing, disruption of RNA structure Clinical use3 clinical trials... 

Ribozyme RNA RNA Cytoplasm Translation arrest, Destruction of RNA Clinical trials... 

Vayda, M.E., C.K. Shewmaker, and J.K. Morelli (1995). Translational arrest in hypoxic potato tubers is correlated with the aberrant association of elongation factor EF-1-alpha with polysomes. Plant Mol. Biol. 28 751-757. 

RNA. In principle, this treatment may lead to translation arrest. In addition, lanthanides and complexes thereof have been reported to cleave RNA by way of a hydrolytic pathway. Recently, a novel europium complex was covalently linked to an oligonucleotide and shown to cleave 88% of the complementary RNA at physiological pH (334). 

Protein translocation across the ER membrane involves the interaction between ribosomes and the signal recognition particle (SRP). SRP is thought to recognize a signal sequence in the nascent protein which causes it to bind tightly to the active ribosome (1,2). This in turn provokes translational arrest, followed by the targeting of the dormant ribosome/SRP complex to the SRP receptor in the ER membrane. 

There are two main mechanisms (19) by which microbes become resistant (a) bacterial ribosomes may become resistant to translational arrest by tetracyclines and (b) tetracyclines may be pumped out of the cell by an energy-consuming efflux mechanism. Neither mechanism involves chemical modification of the drug. 

---