IGFBP7
Insulin-like growth factor-binding protein 7 is a protein that in humans is encoded by the IGFBP7 gene. The major function of the protein is the regulation of availability of insulin-like growth factors (IGFs) in tissue as well as in modulating IGF binding to its receptors. IGFBP7 binds to IGF with low affinity compared to IGFBPs 1-6. It also stimulates cell adhesion. The protein is implicated in some cancers. Interactions IGFBP7 has been shown to interact with Insulin-like growth factor 1, VPS24, and the IGF-1 receptor (IGF1R). RNA Editing The pre-mRNA of this protein is subject to RNA editing. The two editing sites were previously recorded as single nucleotide polymorphisms in dbSNP. Editing type A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine. Inosines are recognised as guanosine by the cell's translational machinery. There are three members of the ADAR family ADARs 1-3 with ADAR 1 and ADAR 2 being the only enzymatically active members. ADAR3 is thought to have a regulatory role in the brain. ADAR1 and ADAR 2 are widely expressed in tissues while ADAR 3 is restricted to the brain. The double stranded regions of RNA are formed by base-pairing between residues in the close to region of the editing site with residues usually in a neighboring intron but can be an exonic sequence. The region that base pairs with the editing region is known as an Editing Complentary Sequence (ECS). It is thought that the pre-mRNA of IGFBP7 is a substrate for ADAR1 based on the expression spectrum of the editing enzyme. Editing sites The pre-mRNA of this protein is edited at two positions. These editing sites occur within the insulin growth factor domain. R/G site There is an Arginine (R) to a Glycine (G) substitution at amino acid position 78 of the final protein. K/R site There is a K to R substitution at amino acid position 95. The editing complementary sequence (ECS) is located in a region within the coding sequence about 200 base pairs upstream from the editing sites. The ECS forms 140 bp duplex structure. The A to G discrepancies for these two editing sites were confirmed experimentally to be RNA editing by analyzing matched cDNA and genomic dna sequences from the same tissue sample. Intriguingly, those RNAs that do not need an intron sequence to pair with could, in theory, continue to undergo editing as mature mRNA. A third candidate editing site did not show evidence of RNA editing in sequence analysis, which may be an indication that either the RNA editing process is tissue specific, or editing occurs at a low frequency. One other possible explanation is that these edits are related to specific genomic polymorphisms. The editing site also overlaps with an antisense transcript which could also form a double stranded RNA structure creating a suitable substrate for ADARs. Editing regulation Editing is observed in a wide range