MRNA instability

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-... 

The analysis of the predictive role of TS polymorphisms may be more complex if the 6-bp deletion/insertion (del/ins) polymorphism in the 3 UTR is added for consideration. The 6-bp deletion allele may cause mRNA instability and reduce intratumoral TS mRNA levels (32). The improved study design on the pharmacogenetic effect of TS polymorphisms should include a global evaluation of the combined VNTR, G/C, and 6-bp del/ins polymorphisms (33). The same global analysis applies to other genes, especially when the functional polymorphism is unclear. Haplotypes may be more informative than individual genotypes. Haplotype tag SNPs (htSNPs) based on the international HapMap project may represent the next wave of pharmacogenomic studies. 

Tierney, M.J. and Medcalf, R.L. (2001) Plasminogen Activator Inhibitor Type 2 Contains mRNA Instability Elements within Exon 4 of the Coding Region. J. Biol. Chem., 276, 13675-13684. 

The 3 UTR is defined as the mRNA sequences following the termination codon. The 3 UTR is thought to play a potential role in mRNA stability. AU-rich motifs are commonly found in the 3 UTR of mRNA of cytokines, growth factors and oncogenes. These motifs are mRNA instability elements and should be... 

J. M. Di Noia, I. D Orso, D. O. Sanchez, and A. C. C. Frasch, AU-rich elements in the 3 -untranslated region of a new mucin-type family of Trypanosoma cruzi confers mRNA instability and modulates translation efficiency, J. Biol. Chem., 275 (2000) 10218—10227. 

Inflammation-Related Diseases by Causing Cytokine mRNA Instability 1214 References 1221... 

POTENTIAL APPLICATIONS OF TRISTETRAPROLIN FAMILY PROTEINS IN INFLAMMATION-RELATED DISEASES BY CAUSING CYTOKINE mRNA INSTABILITY... 

Gil P, Green PJ (1996) Multiple regions of the Arabidopsis SAUR-ACl gene control transcript abundance The 3 untranslated region functions as an mRNA instability determinant. EMBO J 15 1678-1686... 

Genomic DNA is much more complex than cDNA. Since cDNAs are synthesized in the laboratory from mRNAs using reverse transcriptase, they are no more diverse than the number of mRNAs present at the time of isolation. However, only about 2% of the mammalian genome codes for the synthesis of proteins and their mRNAs. Thus genomic DNA libraries are at least 50 times more diverse than cDNA libraries. cDNA libraries are not easier to make, however, both because of the inherent instability of mRNA compared to DNA and because reverse transcriptase prematurely terminates when copying long mRNAs. 

Mandola MV, Stoehlmacher J, Zhang W et al. A 6bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels. Pharmacogenetics 2004 14 319-327. 

Dani C, Blanchard JM, Piechaczyk M, El Sabouty S, Marty L, Jeanteur R Extreme instability of myc mRNA in normal and transformed human cells. Proc Natl Acad Sci USA 1984 81 7046-7050,... 

Unique disadvantages to ribosome display relate to the inherent instability of RNA. This is a disadvantage shared by mRNA display but an advantage of ribosome display over mRNA display is that the in vitro transcription and translation can be combined into one step. This renders the mRNA less vulnerable to degradation. 

Two groups, one [22] taking an in vitro-based biochemical approach, the other [54] performing functional studies, investigated the cellular mechanism of RISC-siRNA interactions and found that the absolute and relative instabilities of the base pairs at the ends of the siRNA duplex determine which strand (i.e., antisense or sense) interacts with RISC and guides subsequent cleavage of complementary mRNA sequences. The relatively low stabihty of the 5 antisense end of functional siRNA du-... 

These mutant alleles fail to produce receptor proteins cells carrying these mutations do not bind any LDL in saturable fashion. This phenotype arises from point mutations causing premature termination codons early in the protein-coding region, mutations in the promoter region that block transcription, mutations that lead to abnormal splicing and/or instability of the mRNA, and large deletions. 

Both ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs)are synthesized in the form of larger transcripts (pre-rRNA and pre-tRNA, respectively), which undergo cleavage at both ends of the transcript, en route to becoming mature RNAs. The total amount of DNA encoding these RNAs amounts to less than 1% of the E. coli genome, but because of the instability of mRNA (which is encoded by the remaining 99%), rRNA and tRNA constitute about 98% of the total RNA in a bacterial cell. 

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