PT  - JOURNAL ARTICLE
AU  - Jeetayu Biswas
AU  - Vivek L. Patel
AU  - Varun Bhaskar
AU  - Jeffrey A. Chao
AU  - Robert H. Singer
AU  - Carolina Eliscovich
TI  - The structural basis for RNA selectivity by the IMP family of RNA binding proteins
AID  - 10.1101/618587
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 618587
4099  - http://biorxiv.org/content/early/2019/08/12/618587.short
4100  - http://biorxiv.org/content/early/2019/08/12/618587.full
AB  - The Igf2 mRNA binding proteins (ZBP1/IMP1, IMP2, IMP3) are highly conserved post-transcriptional regulators of RNA stability, localization and translation. They play important roles in cell migration, neural development, metabolism and cancer cell survival. The knockout phenotypes of individual IMP proteins suggest that each family member regulates a unique pool of RNAs, yet evidence and an underlying mechanism for this is lacking. Here, we combine SELEX and NMR spectroscopy to demonstrate that the major RNA binding domains of the two most distantly related IMPs (ZBP1 and IMP2) bind to different consensus sequences and regulate targets consistent with their knockout phenotypes and roles in disease. We find that the targeting specificity of each IMP is determined by few amino acids in their variable loops. As variable loops often differ amongst KH domain paralogs, we hypothesize that this is a general mechanism for evolving specificity and regulation of the transcriptome.