Repression Translation

Petersen, C. P., Bordeleau, M. E., Pelletier, J., and Sharp, P. A. (2006). Short RNAs repress translation after initiation in mammalian cells. Mol. Cell 21, 533—542. 

One of the most prominent features of the 50S subunit is the LI protuberance, seen on the left side in Fig. 29-6A. This protuberance is formed almost entirely by protein LI, which is one of the largest ribosomal proteins. It binds to the 2105-2184 loop in domain V of the 23S RNA (see Fig. 29-14).139 LI has an important regulatory role in bacteria in which it represses translation of its own structural gene by binding to a region in its mRNA close to the Shine-Dalgamo sequence. 

Proteins Mainly by Enhancing Transcript Stability or Repressing Translation... 

Micro RNAs Repress Translation of Specific mRNAs... 

Both miRNAs and siRNAs contain 21-23 nucleotides, are generated from longer precursor molecules, and are assembled into a multiprotein RNA-induced silencing complex (RISC) that either represses translation of target mRNAs or cleaves them (see Figure 12-27). 

Cytoplasmic polyadenylation is required for translation of mRNAs with a short poly(A) tall. Binding of a specific protein to regulatory elements In their 3 UTRs represses translation of these mRNAs. Phosphorylation of this RNA-binding protein, induced by an external signal, leads to lengthening of the 3 poly (A) tall and translation (see Figure 12-28). 

Saxena S, Jonsson Z O, Dutta A (2003). Small RNAs with imperfect match to endogenous mRNA repress translation. Implications for off-target activity of small inhibitory RNA in mammalian cells. /. Biol. Chem. 278 44312-44319. 

The two species are quite similar the variations come from their source. MicroRNA comes from short endogenous hairpin loop structures, while siRNA molecules are produced from long double-stranded RNA molecules or giant hairpin molecules. The mature miRNA molecules are 22 nucleotide duplexes and usually repress translation of target mRNA sequences. The siRNAs are part of the antiviral defense system of the cell. 

EXAMPLE 9.43 In 2006, a Nobel Prize was awarded for the discovery of RNA interference (RNAi). This is an exquisitely specific and sensitive process in which double-stranded RNA (dsRNA) guides distinct nucleases to degrade only mRNA that shares its sequence. As dsRNA is not a normal component of the transcriptome, it is believed that RNAi is part of a genome surveillance system that is used to repress transposons and viruses that have dsRNA as part of their replication cycle. Similar short sequences of RNA, called microRNAs, repress translation when they are bound to almost-complementary sequences in the 3 untranslated region of mRNA. 

Should this as yet unproven view be correct, two types of translational inhibitor should be clearly distinguished. The first comprises the various kinases that phosphorylate the a-subunit of eIF-2 and are controlled by heme or activated by dsRNA or other conditions (Section 7.4). These kinases repress translation because they cause elF-2 to be phosphorylated. The second type of inhibitor is phosphorylated eIF-2 itself, which, by competing with active eIF-2 for the GDP/GTP exchange factor, eIF-2B, depletes the pool of recycling eIF-2B as just suggested and prevents recycling of eIF-2. The observation that phosphorylated eIF-2 is able to stimulate translation in heme-deficient lysates (Safer et ai, 1977 Benne et al., 1980) is not at variance with this view, because the observed effect concerns non-catalytic functioning of eIF-2. 

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