Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2).

RNA editing in brain controls a determinant of ion flow in glutamate-gated channels.

Zinc enzymology is, compared to some other current areas of metallobiochemistry, a maturing field, but in addition to further developments of structure-function relationships it has also provided a number of surprising new results and ideas in the last few years. In fact, the number of studies makes it impossible to provide a comprehensive review of the recent literature on zinc enzymology here, and the authors therefore focus on those zinc enzymes for which structure-function relationships are possible on the basis of structural and biochemical data. This means that, with a few exceptions, only zinc enzymes for which NMR or crystal structures are available are included here. Another seemingly simple, yet experimentally sometimes complex issue concerns the choice of which metalloenzyme is a zinc enzyme. Since there is in principle no difference in chemical catalysis by low-affinity compared to high-affinity metal sites, some of these enzymes are also included in this article, especially if they are or have been discussed as zinc enzymes, or are active with zinc. 552 refs.

Recent Advances in Zinc Enzymology

http://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/181236/1/yigak02148.pdf

Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells.

DNA methylation is one of the best-characterized epigenetic modifications and has been implicated in numerous biological processes, including transposable element silencing, genomic imprinting and X chromosome inactivation. Compared with other epigenetic modifications, DNA methylation is thought to be relatively stable. Despite its role in long-term silencing, DNA methylation is more dynamic than originally thought as active DNA demethylation has been observed during specific stages of development. In the past decade, many enzymes have been proposed to carry out active DNA demethylation and growing evidence suggests that, depending on the context, this process may be achieved by multiple mechanisms. Insight into how DNA methylation is dynamically regulated will broaden our understanding of epigenetic regulation and have great implications in somatic cell reprogramming and regenerative medicine.

/pdf/active-dna-demethylation-many-roads-lead-to-rome-4b7mplg1mx.pdf

Active DNA demethylation: many roads lead to Rome

The p27 catalytic subunit of the apolipoprotein B mRNA editing enzyme is a cytidine deaminase.

Evolutionary origins of apoB mRNA editing: catalysis by a cytidine deaminase that has acquired a novel RNA-binding motif at its active site.

Apolipoprotein (apo) B100 mRNA undergoes editing of C-6666 to a U residue, which generates a stop-translation codon and defines the carboxyl terminus of apoB48. To aid purification of the editing enzyme we have undertaken UV crosslinking of a 32P-labeled substrate for apoB mRNA editing in vitro to proteins in an enterocyte editing extract. Proteins of 60 (p60) and 43 (p43) kDa, prominent among crosslinking bands, were competed for by unlabeled substrate, but not by nonspecific RNA, and did not crosslink to antisense RNA. Editing in vitro and UV crosslinking were inhibited by NaCl and vanadyl ribonucleoside complexes and by chemical modification of sulfhydryl, imidazolium, and guanidinium groups on the protein. The editing activity copurified predominantly with p60. To define the binding site for p60 on the substrate RNA, a series of scanning and point mutant RNAs, previously used to define nucleotides 6671-6681 as essential for editing, were used in competition studies with wild-type substrate. Results demonstrated that p60 binding is centered on nucleotides 6671-6674. We suggest that p60 contains the RNA-recognition component of the apoB mRNA-editing enzyme.

Apolipoprotein B mRNA editing is associated with UV crosslinking of proteins to the editing site.

Characterization of the rodent genes for arylacetamide deacetylase, a putative microsomal lipase, and evidence for transcriptional regulation.

Human intestinal apolipoprotein (apo) B mRNA undergoes a C to U RNA editing at nucleotide 6666 to generate a translation stop at codon 2153, which defines the carboxy-terminal of apo B48. Here we show that two of eleven human intestinal cDNAs spanning residue 6666 were edited from a genomically-encoded C to a T at residue 6802 as well as at residue 6666. This additional editing converts Thr (ACA) codon 2198 to Ile (AUA). Synthetic RNA including the nucleotide 6802 was edited in vitro by intestinal extracts at 10-15% of the editing efficiency of nucleotide 6666. A sequence is identified as important for recognition by the editing activity. No secondary structural homology was identified between the two edited sites. No other sequence in the region between 6411 and 6893 nucleotides of apo B mRNA was found to be edited in vivo or in vitro. Apo B RNA editing extracts from intestine did not edit maize cytochrome oxidase II mRNA.

Dipti Patel

Papers

The p27 catalytic subunit of the apolipoprotein B mRNA editing enzyme is a cytidine deaminase.

Evolutionary origins of apoB mRNA editing: catalysis by a cytidine deaminase that has acquired a novel RNA-binding motif at its active site.

Apolipoprotein B mRNA editing is associated with UV crosslinking of proteins to the editing site.

Characterization of the rodent genes for arylacetamide deacetylase, a putative microsomal lipase, and evidence for transcriptional regulation.

An additional editing site is present in apolipoprotein B mRNA