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Gray MW 《Biochemistry》2012,51(26):5235-5242
The term "RNA editing" encompasses a wide variety of mechanistically and phylogenetically unrelated processes that change the nucleotide sequence of an RNA species relative to that of the encoding DNA. Two general classes of editing, substitution and insertion/deletion, have been described, with all major types of cellular RNA (messenger, ribosomal, and transfer) undergoing editing in different organisms. In cases where RNA editing is required for function (e.g., to generate a translatable open reading frame in a mRNA), editing is an obligatory step in the pathway of genetic information expression. How, when, and why individual RNA editing systems originated are intriguing biochemical and evolutionary questions. Here I review briefly what is known about the biochemistry, genetics, and phylogenetics of several very different RNA editing systems, emphasizing what we can deduce about their origin and evolution from the molecular machinery involved. An evolutionary model, centered on the concept of "constructive neutral evolution", is able to account in a general way for the origin of RNA editing systems. The model posits that the biochemical elements of an RNA editing system must be in place before there is an actual need for editing, and that RNA editing systems are inherently mutagenic because they allow potentially deleterious or lethal mutations to persist at the genome level, whereas they would otherwise be purged by purifying selection.  相似文献   

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Queuine can replace guanine in the anticodon of certain tRNAs and is a hypermodified guanine derivative that can be synthesized by bacteria but not by mice. The study demonstrates that Drosophila can incorporate dietary queuine into tRNA but cannot synthesize it de novo for this purpose. Since an earlier study had shown that dietary CdCl2 caused Drosophila to increase greatly the proportion of queuine-containing tRNA over non-queuine tRNA the ability of dietary queuine to counteract cadmium toxicity was evaluated. When queuine was present in the cadmium-containing medium more pupae matured into adults than when queuine was absent. Other studies had demonstrated that the transglycosylase enzyme, that catalyzes the replacement of guanine in the anticodon of tRNA by queuine, is present in Drosophila larvae but the tRNA is virtually devoid of queuine. This study shows that in the presence of dietary queuine the larval tRNA contains abundant amounts of queuine. Therefore, we postulate a significant role for bacteria in supplying queuine to Drosophila for its incorporation into tRNA and that the control of this process by Drosophila is passive, i.e. is not an essential feature in differentiation.  相似文献   

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Huang C  Wu G  Yu YT 《Nature protocols》2012,7(4):789-800
Isomerization from uridine to pseudouridine (pseudouridylation) is largely catalyzed by a family of small ribonucleoproteins called box H/ACA RNPs, each of which contains one unique small RNA-the box H/ACA RNA. The specificity of the pseudouridylation reaction is determined by the base-pairing interactions between the guide sequence of the box H/ACA RNA and the target sequence within an RNA substrate. Thus, by creating a new box H/ACA RNA harboring an artificial guide sequence that base-pairs with the substrate sequence, one can site-specifically introduce pseudouridines into virtually any RNA (e.g., mRNA, ribosomal RNA, small nuclear RNA, telomerase RNA and so on). Pseudouridylation changes the properties of a uridine residue and is likely to alter the role of its corresponding RNA in certain cellular processes, thereby enabling basic research into the effects of RNA modifications. Here we take a TRM4 reporter gene (also known as NCL1) as an example, and we present a protocol for designing a box H/ACA RNA to site-specifically pseudouridylate TRM4 mRNA. Disease-related mutation can result in early termination of translation by creating a premature termination codon (PTC); however, pseudouridylation at the PTC can suppress this translation termination (nonsense suppression). Thus, the experimental procedures described in this protocol may provide a novel way to treat PTC-related diseases. This protocol takes 10-13 d to complete.  相似文献   

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Partially purified extracts from Chlorella pyrenoidosa and Chlamydomonas reinhardtii catalyze the cleavage of queuosine (Q), a modified 7-deazaguanine nucleoside found exclusively in the first position of the anticodon of certain tRNAs, to queuine, the base of Q. This is the first report of an enzyme that specifically cleaves a 7-deazapurine riboside. Guanosine is not a substrate for this activity, nor is the epoxide a derivative of Q. We also establish that both algae can incorporate exogenously supplied queuine into their tRNA but lack Q-containing tRNA when cultivated in the absence of queuine, indicating that they are unable to synthesize Q de novo. Although no physiological function for Q has been identified in these algae, Q cleavage to queuine would enable algae to generate queuine from exogenous Q in the wild and also to salvage (and recycle) queuine from intracellular tRNA degraded during the normal turnover process. In mammalian cells, queuine salvage occurs by the specific cleavage of queuine from Q-5'-phosphate. The present data also support the hypothesis that plants, like animals, cannot synthesize Q de novo.  相似文献   

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Queuine, a modified form of 7-deazaguanine present in certain transfer RNAs, is shown to occur in Drosophila melanogaster adults in a free form and its concentration varies as a function of age, nutrition and genotype. In several, but not all mutant strains, the concentrations of queuine and the Q(+) (queuine-containing) form of tRNATyr are correlated. The bioassay employs L-M cells which respond to the presence of queuine by an increase in their Q(+)tRNAAsp that is accompanied by a decrease in the Q(-)tRNAAsp isoacceptors. The increase in Q(+)tRNATyr in Drosophila that occurs on a yeast diet is accompanied by an increase in queuine. Similarly the increase of Q(+)tRNAs with age also is accompanied by an increase in free queuine. In two mutants, brown and sepia, these correlations were either diminished or failed to occur. Indeed, the extract of both mutants inhibited the response of the L-M cells to authentic queuine. When the pteridines that occur at abnormally high levels in sepia were used at 1 x 10(-6)M, the inhibition of the L-M cell assay occurred in the order biopterin greater than pterin greater than sepiapterin. These pteridines were also inhibitory for the purified guanine:tRNA transglycosylase from rabbit but the relative effectiveness then was pterin greater than biopterin greater than sepiapterin. Pterin was competitive with guanine in the enzyme reaction with Ki = 0.9 x 10(-7)M. Also when an extract of sepia was chromatographed on Sephadex G-50, the pteridine-containing fractions only were inhibitory toward the L-M cell assay or the enzyme assay. These results indicate that free queuine occurs in Drosophila but also that certain pteridines may interfere with the incorporation of queuine into RNA.  相似文献   

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Background

In plant organelles, specific messenger RNAs (mRNAs) are subjected to conversion editing, a process that often converts the first or second nucleotide of a codon and hence the encoded amino acid. No systematic patterns in converted sites were found on mRNAs, and the converted sites rarely encoded residues located at the active sites of proteins. The role and origin of RNA editing in plant organelles remain to be elucidated.

Results

Here we study the relationship between amino acid residues encoded by edited codons and the structural characteristics of these residues within proteins, e.g., in protein-protein interfaces, elements of secondary structure, or protein structural cores. We find that the residues encoded by edited codons are significantly biased toward involvement in helices and protein structural cores. RNA editing can convert codons for hydrophilic to hydrophobic amino acids. Hence, only the edited form of an mRNA can be translated into a polypeptide with helix-preferring and core-forming residues at the appropriate positions, which is often required for a protein to form a functional three-dimensional (3D) structure.

Conclusion

We have performed a novel analysis of the location of residues affected by RNA editing in proteins in plant organelles. This study documents that RNA editing sites are often found in positions important for 3D structure formation. Without RNA editing, protein folding will not occur properly, thus affecting gene expression. We suggest that RNA editing may have conferring evolutionary advantage by acting as a mechanism to reduce susceptibility to DNA damage by allowing the increase in GC content in DNA while maintaining RNA codons essential to encode residues required for protein folding and activity.  相似文献   

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