biostudies-literatureDagil RCancer Research UKWellcome trustMedical Research CouncilThe Francis Crick InstituteWellcome Trust4334-4348https://www.ebi.ac.uk/biostudies/studies/S-EPMC6486635biostudies-literatureUnknown47(8)IGF2 mRNA-binding protein 1 (IMP1) is a key regulator of messenger RNA (mRNA) metabolism and transport in organismal development and, in cancer, its mis-regulation is an important component of tumour metastasis. IMP1 function relies on the recognition of a diverse set of mRNA targets that is mediated by the combinatorial action of multiple RNA-binding domains. Here, we dissect the structure and RNA-binding properties of two key RNA-binding domains of IMP1, KH1 and KH2, and we build a kinetic model for the recognition of RNA targets. Our data and model explain how the two domains are organized as an intermolecular pseudo-dimer and that the important role they play in mRNA target recognition is underpinned by the high RNA-binding affinity and fast kinetics of this KH1KH2-RNA recognition unitNucleic acids researchIMP1 KH1 and KH2 domains create a structural platform with unique RNA recognition and re-modelling properties.PMC648663510029MC_U117574558FC001029U117574558FC001178MC_PC_130511017810015Taylor IADagil RHobor FKelly GBall NJPurkiss AGRamos AMartin SROgrodowicz RWfalseIMP1 KH1 and KH2 domains create a structural platform with unique RNA recognition and re-modelling properties.IGF2 mRNA-binding protein 1 (IMP1) is a key regulator of messenger RNA (mRNA) metabolism and transport in organismal development and, in cancer, its mis-regulation is an important component of tumour metastasis. IMP1 function relies on the recognition of a diverse set of mRNA targets that is mediated by the combinatorial action of multiple RNA-binding domains. Here, we dissect the structure and RNA-binding properties of two key RNA-binding domains of IMP1, KH1 and KH2, and we build a kinetic model for the recognition of RNA targets. Our data and model explain how the two domains are organized as an intermolecular pseudo-dimer and that the important role they play in mRNA target recognition is underpinned by the high RNA-binding affinity and fast kinetics of this KH1KH2-RNA recognition unit2019-01-01T00:00:00Z2019 May2026-04-30T02:36:59.327Z2019-06-06T22:50:10ZS-EPMC64866353086466010.1093/nar/gkz136