Translational repression

In the cell, messenger RNA does not exist as free molecules, but appears to be complexed with protein in messenger ribonucleoprotein 

In the surf clam, however, there is compelling evidence that fertilization results in the selective activation of translation of specific mRNA species (Rosenthal et al., 1980). mRNA extracted before and after fertilization gave identical patterns of protein synthesized upon translation in the RNA-dependent reticulocyte lysate, while homogenates from fertilized eggs showed the appearance and extensive synthesis of novel proteins, and decreased synthesis of others, when compared to homogenates from oocytes. Clearly, the translational repression active in the clam oocyte acts in an mRNA-specific man- 

In muscle development, a number of myofibrillar proteins appears at specific stages of differentiation. There is evidence that expression of myosin heavy chain mRNA may involve its synthesis and storage as mRNP before the mRNA is mobilized into polysomes at a specific stage (Buckingham et al., 1974 Heywood and Rich, 1968 Jain and Sarkar, 1979), but the data are not yet as convincing as in the previous examples. 

Another example of mRNA masking is suggested by the iron-induced synthesis of ferritin. In reticulocytes of the bullfrog tadpole, synthesis of ferritin increases 40- to 50-fold in the presence of iron, while the level of ferritin mRNA, translatable after extraction in the 

A number of reports describe low-molecular weight RNAs that inhibit mRNA translation, usually in a nonspecific manner, but their relevance to translational control remains to be demonstrated (see Austin and Kay, 1982). 

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Dalby, B., and Glover, D. M. (1993). Discrete sequence elements control posterior pole accumulation and translational repression of maternal cyclin B RNA in Drosophila. EMBOJ. 12 1219-1227. 

Mazroui, R., Huot, M. E., Tremblay, S., Filion, C., Labelle, Y., and Khandjian, E. W. (2002). Trapping of messenger RNA by Fragile X Mental Retardation protein into cytoplasmic granules induces translation repression. Hum. Mol. Genet. 11, 3007—3017. 

Example experiments using the previous methodologies are shown in Fig. 6.1. The major mRNA constructs described in this chapter are dia-grammatically represented in Fig. 6. IB and an example of in vitro transcribed and polyadenylated R-luc-4 sites mRNA is shown in Fig. 6.1A. In these experiments, translation of R-luc-4 sites mRNA is synergistically promoted by the physiological cap structure and the poly (A) tail (Fig. 6.1C), and full miR-dependent translational repression requires the presence of both modifications (Fig. 6.ID, Humphreys etal., 2005). (TheEMCV IRES-containing constructs are discussed later.)... 

Bhattacharyya, S. N., Habermacher, R., Martine, U., Closs, E. I., and Pilipowicz, W. (2006). Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell 125, 1111-1124. 

Doeneh JG, Sharp PA. Speeificity of microRNA target selection in translational repression. Genes Dev 2004 18 504-511. 

Many Eukaryotic mRNAs Are Subject to Translational Repression... 

Schlax, P.J., Xavier, K. A., Gluick, T. C., and Draper, D. E. (2001). Translational repression of the Escherichia coli alpha operon mRNA Importance of an mRNA conformational switch and a ternary entrapment complex. J. Biol. Chem. 276, 38494-38501. 

WANG, L., WESSLER, S., Inefficient reinitiation is responsible for upstream open reading frame-mediated translational repression of the maize R gene, Plant Cell, 1998,10,1733-1745. 

Morita T, Mochizuki Y, Aiba H. Translational repression is sufficient for gene silencing by bacterial small noncoding RNAs in... 

Morita T, Mochizuki Y, Aiba H. Translational repression is sufficient for gene silencing by bacterial small noncoding RNAs in the absence of mRNA destruction. Proc. Natl. Acad. Sci. U.S.A. 2006 103(13) 4858-4863. 

Translational repression of cad in the anterior region of the Drosophila embryo is affected by the bicoid gene product (Rivera-Pomar and Jackie, 1996 Rivera-Pomar et al., 1996), and this repression is necessary for proper development of anterior structures. Ubiquitous expression of cad early in embryogenesis leads to defects in head formation and segmentation (Mlodzik et al., 1990). Conversely, loss of... 

Niessing, D., Dostatni, N., Jackie, H., Rivera-Pomar, R. 1999. Sequence interval within the PEST motif of Bicoid is important for translational repression of caudal mRNA in the anterior region of the Drosophila embryo. EMBO J. 18, 1966-1973. 

Subsequent biochemical studies with extracts of Drosophila embryos showed that a long double-stranded RNA that mediates interference is initially processed into a double-stranded intermediate referred to as short interfering RNA (siRNA). The strands in siRNA contain 21-23 nucleotides hybridized to each other so that the two bases at the 3 end of each strand are single-stranded. The finding that Dicer ribonuclease is required for formation of siRNAs suggested that RNA interference and miRNA-mediated translational repression are related processes. 

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