RNA Editing IGFBP7

1 rna editing

1.1 editing type
1.2 editing sites

1.2.1 r/g site
1.2.2 k/r site


1.3 editing regulation
1.4 consequences

1.4.1 structural
1.4.2 function
1.4.3 functions in learning , memory

rna editing

the pre-mrna of protein subject rna editing. 2 editing sites recorded single nucleotide polymorphisms in dbsnp.

editing type

a rna editing catalyzed family of adenosine deaminases acting on rna (adars) recognize adenosines within double-stranded regions of pre-mrnas , deaminate them inosine.inosines recognised guanosine cells translational machinery.there 3 members of adar family adars 1-3 adar 1 , adar 2 being enzymatically active members.adar3 thought have regulatory role in brain.adar1 , adar 2 expressed in tissues while adar 3 restricted brain.the double stranded regions of rna formed base-pairing between residues in close region of editing site residues in neighboring intron can exonic sequence.the region base pairs editing region known editing complentary sequence (ecs). thought pre-mrna of igfbp7 substrate adar1 based on expression spectrum of editing enzyme.

editing sites

the pre-mrna of protein edited @ 2 positions.these editing sites occur within insulin growth factor domain.

r/g site

there arginine (r) glycine (g) substitution @ amino acid position 78 of final protein.

k/r site

there k r substitiution @ amino acid position 95.

the editing complementary sequence (ecs) located in region within coding sequence 200 base pairs upstream editing sites.the ecs forms 140 bp duplex structure. g discrepancies these 2 editing sites confirmed experimentally rna editing analyzing matched cdna , genomic dna sequences same tissue sample. intriguingly, rnas not need intron sequence pair could, in theory, continue undergo editing mature mrna. third candidate editing site did not show evidence of rna editing in sequence analysis, may indication either rna editing process tissue specific, or editing occurs @ low frequency. 1 other possible explanation these edits related specific genomic polymorphisms. editing site overlaps antisense transcript form double stranded rna structure creating suitable substrate adars.

editing regulation

editing observed in wide range of tissues. editing @ k/r site @ amino acid position 95 high in human brain.

consequences
structural

the edited sites found within insulin growth factor binding domain of igfbp7 , heparin binding domain.this region site proteolytic cleavage.structural analysis of edited sites determined 2 amino acids corresponded edited sites not directly involved in binding igf-1 found in regions flanking them. @ position 78 in unedited version of transcript there arginine close residue valine-49.this valine important in hydrophobic interaction of phenylalanine of igf-1.a substitution glycine @ position thought introduce additional flexibility leading change of loop conformation, thereby disrupting hydrophobic interaction stabilises complex. @ amino acid position 98 unedited transcript contains lysine .this residue makes non specific interactions via aliphatic part of side chain glu-38 of igf-1.in edited version position arginine.the long side chain of thought able maintain these weak interactions

function

the edited region contains proposed heparin binding site , part of recognition sequence proteolytic cleavage.heparin binding inhibits cell binding , cell adhesion functions of protein. cleavage occurs @ amino acid position 97 reduces heparin binding modulates growth stimulatory activity of protein. since editing site occurs within proposed heparin binding region effects of editing may have implications heparin binding , proteolytic clevage , therefore have other affects downstream.since protein has been implicated in these processes believed editing might effect apoptosis, regulation of cell growth , angiogenesis.

functions in learning , memory

a study @ european neuroscience institute-goettingen (germany) found fear extinction-induced igf2/igfbp7 signalling promotes survival of 17- 19-day-old newborn hippocampal neurons. suggests therapeutic strategies enhance igf2 signalling , adult neurogenesis might suitable treat diseases linked excessive fear memory such ptsd. same group has found igfbp7 levels increased in alzheimer s disease , regulated via dna methylation. elevation of igfbp7 in wild type mice causes memory impairment. blocking igfbp7 function in mice develop alzheimer s disease-like memory impairment restores memory function. these data suggest igfbp7 critical regulator of memory consolidation , might used biomarker alzheimer s disease. targeting igfbp7 novel therapeutic avenue treatment of alzheimer s disease patients.