3 -untranslated region binding

We concluded that IRPs interact selectively with the APP transcript. These data provided strong genetic support for an integral role for the involvement APP holoprotein in iron metabolism. The fact that IRP-1/IRP-2 are the cognate APP 5 untranslated region binding partners will prove useful for screening novel lead compounds that limit APP translation, particularly if IRP-1 and IRP-2 expression can be functionally linked to APP expression. 

MK2 (also termed MAP kinase-activated protein kinase 2, MAPKAP-K2) is activated by p38 MAP kinase a// (Kotlyarov et al, 2002 Roux and Blenis, 2004). MK2 plays a key role in the control of the production of certain cytokines, for example, tumor necrosis factor a. MK2 does so by phosphorylating proteins that bind specifically to the regulatory regions in the S untranslated regions (UTRs) of such mRNAs (Hitti et al, 2006). These regions contain AU-rich elements (AREs) to which proteins such as HnRNP A1 also bind. 

The small ribosomal subunit binds to the mRNA. In prokaryotes, the 16S rRNA of the small subunit binds to the Shine-Dalgamo sequence in the 5 untranslated region of the niRNA. In eukaryotes, the small subunit binds to the 5 cap structure and slides down the message to the first AUG. 

Gene expression may be controlled by transcription factors that bind to the 5 -untranslated region, which encompasses the promoter. 

Some proteins bind directly to mRNA and act as translational repressors, many of them binding at specific sites in the 3 untranslated region (3 UTR). So positioned, these proteins interact with other translation initiation factors bound to the mRNA or with the 40S ribosomal subunit to prevent translation initiation (Fig. 28-32 compare this with Fig. 27-22). 

Czyzyk-Kreska, M.F., Z. Dominski, R. Kole, and D.E. Millhom (1994). Hypoxia stimulates binding of a cytoplasmic protein to a pyrimidine-rich sequence in the 3 -untranslated region of rat tyrosine hydroxylase mRNA. J. Biol. Chem. 269 9940-9945. 

Iron regulatory proteins (IRPs) regulate the cellular iron level in mammalian cells. IRPs are known as cytosol mRNA binding proteins which control the stability or the translation rate of mRNAs of iron metabolism-related proteins such as TfR, ferritin, and 5-aminolevulinic acid synthetase in response to the availability of cellular iron [19-21] after uptake [5]. The regulatory mechanism involves the interaction between the iron-responsive element (IRE) in the 3 or 5 untranslated regions of the transcripts and cytosolic IRPs (IRP-1 and -2). IRP-1 is an iron-sulfur (Fe-S) protein with aconitase activity containing a cubane 4Fe-4S cluster. When Fe is replete, IRP-1 prevails in a 4Fe-4S form as a holo-form and is an active cytoplasmic aconitase. As shown in Fig. 3, when Fe is deplete, it readily loses one Fe from the fourth labile Fe in the Fe-S cluster to become a 3Fe-4S cluster and in this state has little enzymatic activity [22, 23]. 

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