MRNA translational control

This article focuses on how the marked increase in the steady-state levels of metals (iron, copper and zinc) in the AD brain contributes to gene expression with deleterious consequences for neuronal survival [3]. Certainly APP mRNA translational control by iron (Rogers et al., 2002) and APP gene transcriptional control by copper [1] each provide new genetic support for the model that APP is a metalloprotein with an integral role in metal metabolism. 

Figure 2. Model for Ferritin mRNA Translational Control Iron releases IRP-l/IRP-2 from suppressing ferritin mRNA translation at the Iron responsive Element stemloops (IREs) specific to the L- and H- mRNA 5 cap sites. In the diagram, IRP-I and IRP-2 are depicted as two domains separated by a hinge region (line). Our preliminary data suggests that the RNA binding protein (Poly C-binding proteins, CP-1 and CP-2) interact with the ferritin mRNA acute box(AB) domain (box) downstream from the IRE (Thomson et al. In revision).

Vassalli, J. D., Huarte, J., Belin, D., Gubler, P., Vassalli, A., O Connell, M. L., Parton, L. A., Rickies, R. J., and Strickland, S. (1989). Regulated polyadenylation controls mRNA translation during meiotic maturation of mouse oocytes. Genes Dev. 3 2163-2171. 

Schwab MS, Kim SH, Terada N et al 1999 The p70(S6K) controls selective mRNA translation during oocyte maturation and early embryogenesis in Xenopus laevis. Mol Cell Biol 19 2485— 2494... 

Methods to Analyze MicroRNA-Mediated Control of mRNA Translation... 

Both the overall rate of protein synthesis and the translation of certain specific mRNAs are controlled by agents such as hormones, growth factors, and other extracellular stimuli. As precursors for protein assembly, amino acids also regulate the translational machinery. Because protein synthesis consumes a high proportion of cellular metabolic energy, the energy status of the cell also modulates translation factors. 

Despite the fluctuations in p27 protein levels during the cell cycle, the amount of p27 mRNA remains unchanged. Instead, p27 protein levels are regulated through translational controls (Hengst and Reed, 1996 Millard et... 

Successful expression depends on several factors, such as efficiency of delivery of vector DNA to the host cell, transcriptional and translational control elements on the vector, mRNA stability, genetic... 

Another way in which gene expression is regulated is by translational control, where the rate of protein synthesis is controlled at the point of transcription of mRNA into polypeptides (Appendix 5.6). Generally, the majority of the control mechanisms in bacteria is at the transcriptional level. Translational control is less well understood and appears to be a secondary mechanism in bacteria, but it is thought to be very important in eukaryotic organisms. 

The synthesis of ribosomal proteins is regulated at the level of translation. Certain ribosomal proteins bind to specific sites on the ribosomal RNAs or their own mRNAs. In the absence of the ribosomal RNAs, they bind to their own mRNAs, which inhibits their translation. This form of translational control regulates the rate of synthesis of ribosomal proteins so that it does not exceed the rate of ribosomal RNA synthesis. 

Hinnebusch, A. G., Involvement of an initiation factor and protein phosphorylation in translational control of GCN4 mRNA. Trends Biochem. Sci. 15 148-152, 1990. 

The 5 and 3 UTRs of eukaryotic mRNA are crucial for the regulation of gene expression by controlling mRNA translational efficiency, stability, and localization. The 5 cap and poly A (pA), found on almost all eukaryotic mRNAs, stimulate translation initiation and stabilize mRNA in synergy. However, for in vitro translation, the use of 5 cap and pA can be a major problem, as described Chapter 11 by Endo and Sawasaki. These problems have been effectively overcome by optimizing the 5 and 3 UTRs (12). 

Gallie, D. R. (1996) Translational control of cellular and viral mRNAs. Plant Mol. Biol. 32, 145-158. 

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