6533b830fe1ef96bd12967d5

RESEARCH PRODUCT

Structural Characterization of Set1 RNA Recognition Motifs and their Role in Histone H3 Lysine 4 Methylation

subject

description

Departament de Bioquimica iBiologia Molecular, Universitatde Valencia, C/Dr Moliner 50,46100, Burjassot, SpainThe yeast Set1 histone H3 lysine 4 (H3K4) methyltransferase contains, inaddition to its catalytic SET domain, a conserved RNA recognition motif(RRM1). We present here the crystal structure and the secondary structureassignment in solution of the Set1 RRM1. Although RRM1 has the expectedβαββαβ RRM-fold, it lacks the typical RNA-binding features of thesemodules. RRM1 is not able to bind RNA by itself in vitro, but a constructcombining RRM1 with a newly identified downstream RRM2 specificallybinds RNA. Invivo,H3K4 methylation isnot affectedbyapoint mutation inRRM2 that preserves Set1 stability but affects RNA binding in vitro.Incontrast mutating RRM1 destabilizes Set1 and leads to an increase ofdimethylationofH3K4atthe5′-codingregionofactivegenesattheexpenseof trimethylation, whereas both, dimethylation decreases at the 3′-codingregion. Taken together, our results suggest that Set1 RRMs bind RNA, butSet1 RNA-binding activity is not linked to H3K4 methylation.