Editing, RNA

Glutamate s role as a neurotransmitter in the vertebrate retina is reviewed by Barnstable (1993), Brandstatter et al. (1998) and Lo et al. (1998). As the cell bodies of different retinal cell types are in different laminae (Fig. 10), we can assign which general cell types express which glutamate receptor subunits. However, there are different subsets of the same cell class, e.g., there are at least 10 different types of on- and off-bipolars, and multiple subtypes of the other cell classes (Stevens, 1998). Without cell-type markers and double-labelling studies, ISH can not differentiate these. The cones and rods release glutamate onto the bipolar cells only off-bipolars use ionotropic receptors at this synapse on-bipolars use the metabotropic receptor mGluR6 instead. The distribution of NMDA and non-NMDA receptor mRNAs in the retina is summarized in Fig. 10. 

---

Interestingly, the genomic sequences of all AMPA receptor subunits contain a Q codon for this position and the R codon is selectively introduced into the GluR-B pre-mRNA by RNA editing [3]. Additionally, the Q/R site is a critical determinant of current... 

Seeburg PH, Higuchi M, Sprengel R (1998) RNA editing of glutamate receptor channels mechanism and physiology. Brain Res Brain Res Rev 26 217-219... 

RNA-editing is a posttranscriptional mechanism mediated by RNA editases, which results in a site-selective deamination of adenosine to inosine. This alters codons and splicing in nuclear transcripts and thereby alters the structure and function of proteins. 

ADARl Adenosine deaminase acting on RNA 1 Involved in RNA editing... 

The main apohpoprotein of LDL (P-lipopro-tein) is apohpoprotein B (B-lOO) and is found also in VLDL. Chylomicrons contain a truncated form of apo B (B-48) that is synthesized in the intestine, while B-lOO is synthesized in the hver. Apo B-lOO is one of the longest single polypeptide chains known, having 4536 amino acids and a molecular mass of 550,000 Da. Apo B-48 (48% of B-lOO) is formed from the same mRNA as apo B-lOO after the introduction of a stop signal by an RNA editing enzyme. Apo C-1, C-11, and C-111 are smaller polypeptides (molecular mass 7000— 9000 Da) freely transferable between several different hpoproteins. Apo E is foimd in VLDL, HDL, chylomicrons, and chylomicron remnants it accounts for 5— 10% of total VLDL apohpoproteins in normal subjects. 

This is known to be true of globin genes however, because of the possibility of RNA editing, divergence at the amino acid sequence level need not necessarily imply diversity at the DNA sequence level. 

In addition, there is growing evidence for illnesses caused by genes whose product is an RNA molecule, not a protein per se. Also, the protean manifestations of RNA molecules and their modifications (including RNA editing) may contribute to our understanding of disease [82, 101-103],... 

Wang Q, Khillan J, Gadue P, Nishi-kura K. Requirement of the RNA editing deaminase ADAR1 gene for embryonic erythropoiesis. Science 2000 290[5497] 1765—1768. 

Genetic regulation via splice variants and RNA editing further increases receptor heterogeneity the flip/flop versions and the Q/R site 279... 

Genetic regulation via splice variants and RNA editing further increases receptor heterogeneity the flip/flop versions and the Q/R site. Splice variants that impart functional differences and/or different cellular expression patterns have been found for most of the glutamate receptor subunits. The first splice variants to be described were the so-called flip and flop versions of the AMPA... 

Given this combination of internal and C-terminus splice variants and site-specific RNA editing, it appears that four to eight or more mature RNAs can be made from each of the 16 known genes encoding mammalian... 

Higuchi, M., Single, F. N., Kohler, M. et al. RNA editing of AMPA receptor subunit GluRB a base-paired intron-exon structure determines position and efficiency. Cell 75 1361-1370,1993. 

Finally, RNA editing can be involved, as in the case of the amphibian bombesin-like peptides, where nucleotides in the mRNA are changed and the final protein is not a direct reflection of the sequence encoded in the gene. RNA editing is also seen in the glutamate (Ch. 15) and serotonin receptors (Ch. 13 and Ch. 15) and probably will be found elsewhere as detection methods become more sophisticated. 

Visiers, I., Hassan, S. A., and Weinstein, H. (2001) Differences in conformational properties of the second intracellular loop (IL2) in 5HT(2C) receptors modified by RNA editing can account for G protein coupling efficiency. Prot. Eng. 14,409 414. 

HisselR, WissingerB, Schuster W, Brennicke A. RNA editing in plant mitochondria. Science 1989 246 1632-1634. 

Brennicke A, Kuck A. Plant Mitochondria with Emphasis on RNA. Editing and Cytoplasmic Male Sterility, VCH, Weinheim, Germany, 1993. 

Maier RM,ZeltzP, KosselH. BonnardG,Gualberto JM, Grienenberger JM. RNA editing in plant mitochondria and chloroplasts. Plant Mol Biol 1996 32 343-365. 

Extensive RNA editing of U to C in addition to C to U substitution in the rbcL transcripts of hornwort chloroplasts and the origin of RNA editing in green plants." ... 

Anomalous ubiquitin-B molecules are also present in the brains of control subjects, probably indicating a preneurodegenerative stage. The aberrant proteins show a cellular colocalization compatible with alterations at the transcriptional level or dysfunctional posttranscriptional RNA editing (138). 

Although genetic variation in many genes may be associated with differential drug responses, it is also apparent that other factors, such as epigenetics (DNA methylation, interference RNA, RNA editing, histone acetylation/deacetylation. 

RNA editing This process involves insertion, deletion or modification of nucleotides in the pre-mRNA. The result of one or more of these modifications is that the mRNA is sufficiently modified fhat the properties of the proteins that are produced are slightly different in different tissues. A cytidine base can be converted to uracil in mRNA in a reaction catalysed by a deaminase enzyme. This can result... 

FIGURE 2 RNA editing of the transcript of the cytochrome oxidase subunit II gene from Trypanosoma brucei mitochondria, (a) Insertion of four U residues (pink) produces a revised reading frame, (b) A special class of guide RNAs, complementary to the edited product, may act as templates for the editing process. 

A distinct form of RNA editing occurs in the gene for the apolipoprotein B component of low-density... 

FIGURE 3 RNA editing of the transcript of the gene for the changing a Gin codon to a stop codon and producing a truncated... 

Blanc, V. Davidson, N.O. (2003) C-to-U RNA editing mechanisms leading to genetic diversity J. Biol. Chem. 278, 1395-1398. 

Maas, S., Rich, A., Nishikura, K. (2003) A-to-I RNA editing recent news and residual mysteries. J. Biol. Chem. 278, 1391-1394. 

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). 

---