Untranslated mRNA

The existence of the extremely short 5 untranslated mRNA of many halobacterial mRNAs raises the question of the location of the signals for the initiation of translation (equivalent to the Shine-Dal-garno sequences). In some cases it is possible to detect a sequence complementary to the 3 end of the 16S rRNA at the 5 untranslated transcripts [as in the cases of sop (Blanck et al., 1989), the genes coding... 

Marolda, C.L., Valvano, M.A. Promoter region of the Escherichia coli 07-specific lipopolysaccharide gene cluster structural and functional characterization of an upstream untranslated mRNA sequence. J Bacteriol 180 (1998) 3070-3079. 

The mode of inheritance of EPP is complex but has recently been clarified by enzymatic and molecular studies of families. Molecular analysis has identified more than 60 disabling mutations of the FECH gene that are inherited in EPP families in an autosomal dominant pattern. Within these families, FECH activities in patients with overt disease are lower than the half-normal activities in their asymptomatic relatives with the same mutation. Thus a decrease in FECH activity to less than 50% of normal appears to be essential for development of sufficient overproduction of protoporphyrin to produce symptoms. In most families, this further decrease is produced by inheritance of a low expression FECH allele trans to the severe mutation. The low expression allele is a polymorphic FECH variant present in about 10% of the Western European population. Substitution of a T nucleotide by a C nucleotide at a polymorphic site in intron 3 (IVS3-48C/T) enhances use of an alternative splice site, leading to increased formation of an unstable, untranslated mRNA and reduction of FECH expression by about 25%. This pattern of inheritance has been described as autosomal dominant with modulation by expression of the wild type of FECH allele. Uncommon autosomal recessive cases of EPP have also been reported. ... 

In cell lines such as mouse myeloma or Ehrlich ascites tumor cells some 20% of the total cytoplasmic mRNA is not associated with ribosomes but exists in an untranslated state even though deproteinised mRNA prepared from these mRNP particles is perfectly translatable m vitro. A more or less trivial explanation for such untranslated mRNA is that it originates from a small fraction of the cells in which the rate of initiation is very low, e.g. cells in mitosis. A comparison of the products of vitro translation of this mRNA and of the polysomal mRNA renders this explanation less than wholly satisfactory. In extreme cases, the non-translated mRNPs are found to contain an entirely different set of mRNA species from... 

McGarry, T. J. Lindquist, S. (1985). The preferential translation of Drosophila hsp70 mRNA requires sequences in the untranslated leader. Cell 43,903-911. 

Synthesis of the transferrin receptor (TfR) and that of ferritin are reciprocally linked to cellular iron content. Specific untranslated sequences of the mRNAs for both proteins (named iron response elements) interact with a cytosolic protein sensitive to variations in levels of cellular iron (iron-responsive element-binding protein). When iron levels are high, cells use stored ferritin mRNA to synthesize ferritin, and the TfR mRNA is degraded. In contrast, when iron levels are low, the TfR mRNA is stabilized and increased synthesis of receptors occurs, while ferritin mRNA is apparently stored in an inactive form. This is an important example of control of expression of proteins at the translational level. 

Kaneda S, Takeishi K, Ayusawa D et al. Role in translation of a triple tandemly repeated sequence in the 5 -untranslated region of human thymidylate synthase mRNA. Nucleic Acids Res 1987 15 1259-1270. 

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. 

DON also enhances COX-2 mRNA stability.28 Such modulation is usually explained by the presence of multiple copies of AUUUA motif in the 3 -untranslated region (3 -UTR) of COX-2 mRNA, since the AU-rich element (ARE) in the 3 -UTR of an mRNA targets a transcript for rapid degradation.34 To test this possibility a constitutive SV40... 

G-CSF expression is controlled at both the transcriptional and posttranscrip-tional levels. A sequence of 300 nucleotides upstream of the initiation codon is conserved in both the murine and human genes, and this appears to contain three regulatory sites. G-CSF (and some other cytokine genes) may be constitutively transcribed by cells such as blood monocytes, fibroblasts and endothelial cells, but the mRNA may be short-lived (fi/2 < 15 min). The mRNA contains poly-AUUUA sequences in the untranslated region, and this motif is usually associated with mRNA instability. Indeed, such regions have also been identified in mRNA for GM-CSF, IL-1, IL-6, interferons, TNF, some growth factors, c-jun, c-fos, c-myc and c-myb. Upon the addi-... 

Regulation of expression may occur at both the transcriptional and post-transcriptional levels. The mRNA for GM-CSF contains (in common with those of some other cytokines) conserved regulatory sequences in the 3 untranslated region, which may affect its rate of translation. The gene is constitutively transcribed in monocytes, endothelial cells and fibroblasts, but the mRNA is unstable and so does not accumulate to levels sufficient to allow translation into significant amounts of protein. Activation of these cells results in the increased expression of GM-CSF protein, which arises from both an enhanced rate of transcription (as detected in nuclear runoff experiments) and also an increased stability of the mRNA, perhaps by mechanisms analogous to those described above during activation of G-CSF expression ( 2.2.3.1). 

It is a short contiguous reverse-transcribed segment excised from a spliced mRNA. It should contain either the 5 untranslated region (5 UTR) and/or spliced exonic sequence, and/or 3 untranslated region (3 UTR). 

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