MRNA transcripts posttranscriptional

RNA Posttranscriptional Processing Predict the likely effects of a mutation in the sequence (5 )AAUAAA in a eukaryotic mRNA transcript. 

These processes are summarized in Figure 28-1. We have examined several of these mechanisms in previous chapters. Posttranscriptional modification of mRNA, by processes such as alternative splicing patterns (see Fig. 26-19b) or RNA editing (see Box 27-1), can affect which proteins are produced from an mRNA transcript and in what amounts. A variety of nucleotide sequences in an mRNA can affect the rate of its degradation (p. 1020). Many factors affect the rate at which an mRNA is translated into a protein, as well as the posttranslational modification, targeting, and eventual degradation of that protein (Chapter 27). 

IL-10 and IL-4 inhibit cytoldne expression in activated human monocytes, which suggests that IL-4 may inhibit the transcription of the IL-6 gene. IL-10 may inhibit the IL-6 mRNA levels posttranscriptionally, without suppressing promoter activity in human monocytes.IL-10 also inhibits the production of IL-6, IL-12, and TNFa." Reduced IL-6 levels in individuals who are exposed to chromate were reported, pointing to its possible role in negative immunomodulation. Also, nitrite (NO ) induces a decrease of LPS-stimulated IL-1 (3, IL-6, IL-8, and TNFa release from activated alveolar macrophages. ... 

RAR-RXR heterodimer or RXR-RXR homodimer), the activated receptors bind with high affinity to the specific DNA retinoic acid response element (RARE) and effect mRNA transcription. Ultimately, the retinoid response is mediated by primary target genes, by interference with othertranscription factors or by control of certain posttranscriptional actions. 

Messenger RNA processing/modification. Most primary mRNA transcripts in prokaryotes function in translation without further modification. Eukaryotic mRNA transcripts, however, undergo extensive posttranscriptional modifications. 

Polyadenylation is a critical posttranscriptional processing step in the maturation of eukaryotic mRNA [1], The location where the pre-mRNA is cleaved (also known as the poly(A) site) marks the end of a mRNA transcript. Many eukaryotic genes possess two or more poly(A) sites [2-4], and thus are involved in alternative polyadenylation (APA). APA is a powerful pathway that entails the selection of alternate poly(A) sites in a pre-mRNA and leads to the production of multiple mature mRNA isoforms from the same gene, resulting in potential gene expression regulation [1]. 

Increased transcription levels are assumed to result in increased protein synthesis. One approach to reach this goal is to raise the transgene copy number by the use of amplification-promoting sequences derived from a spacer sequence of tobacco ribo-somal DNA [95]. Posttranscriptional processes such as capping, splicing and polya-denylation are important for high protein yields, and it is also important to maximize mRNA stability [84]. 

The primary transcript must undergo extensive posttranscriptional processing inside the nucleus to form the mature mRNA molecule (F ure 1-3-7). These processing steps indude the fol-... 

In conjunction with studies performed by van Leeuwen et al. (135-138), Layfield et al. (263) proposed a novel mechanism that could account for an inhibition of 26S proteasome activity in cases of nonfamilial AD. Mutant forms of ubiquitin may inhibit proteolysis within neurons, predisposing these cells to inclusion formation. Molecular misreading of the UBB gene results in a dinucleotide deletion in UBB mRNA (135-138,264). In AD, an age-related posttranscriptional defect in primary transcript RNA processing may occur, leading to dinucleotide deletions within open reading frames that result in frameshifts and produce abnormal extension proteins, as demonstrated by van Leeuwen and coworkers (138). 

At present, the possible effects of long-term lithium on the absolute levels of Ga and GOj remain unclear— two independent laboratories have not observed any alterations [Hsiao et al. 1993 Li et al. 1991 Masana et al. 1992], whereas another one has reported small but significant decreases in the levels of the Oij, and Oij rat frontal cortex [Colin et al. 1991]. However, long-term lithium administration reduces the mRNA levels of a number of G proteins in rat brain, including a, Oj, and 0 2 (Colin et al. 1991 Li et al. 1991], suggesting that lithium produces complex transcriptional and posttranscriptional effects after long-term administration [see below]. 

A primary transcript is a linear copy of a transcriptional unit—the segment of DNA between specific initiation and termination sequences. The primary transcripts of both prokaryotic and eukaryotic tRNAs and rRNAs are post-transcriptionally modified by cleavage of the original transcripts by ribonucleases. tRNAs are then further modified to help give each species its unique identity. In contrast, prokaryotic mRNA is generally identical to its primary transcript, whereas eukaryotic nrRNA is extensively modified posttranscriptionally. 

Prokaryotic mRNA is generally identical to its primary transcript, whereas eukaryotic mRNA is extensively modified posttranscriptionally. For example, a 7-methyl-guanosine "cap" is attached to the 5-terminal end of the mRNA through a triphosphate linkage by guanylyl-transferase. A long poly-Atail—not transcribed from the DNA—is attached to the 3 -end of most mRNAs. Many eukaryotic mRNAs also contain introns that must be removed to make the mRNA functional. Their removal requires small nuclear RNAs. 

Patema, J.C., Moccetti, T., Mura, A., Feldon, J. and Bueler, H. (2000) Influence of promoter and WHV posttranscriptional regulatory element on AAV-mediated transgene expression in the rat brain. Gene Ther., 7, 1304-1311. Politz, J.C. and Pederson, T. (2000) Review movement of mRNA from transcription site to the nuclear pores. J. Struct. Biol, 129,252-257. 

Between 10% and 20% of expressed genes in a cell are regulated by glucocorticoids. The number and affinity of receptors for the hormone, the complement of transcription factors and coregulators, and posttranscription events determine the relative specificity of these hormones actions in various cells. The effects of glucocorticoids are mainly due to proteins synthesized from mRNA transcribed... 

Thyroid hormone Synthesis of pumps a) Increased gene transcription (through direct interaction of nuclear T3-receptor complex with c/s-regulatory upstream gene element, or secondary to T3 induction of other proteins, or to altered ion fluxes) b) Posttranscriptional effects on mRNA levels c) Translational effects... 

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