TUT4 and the closely related
TUT7 are non-templated
poly(U) polymerases required at different stages of development, and their mis-regulation or mutation has been linked to important
cancer pathologies. While TUT4(7) interaction with its
pre-miRNA targets has been characterized in detail, the molecular bases of the broader target recognition process are unclear. Here, we examine
RNA binding by the ZnF domains of the
protein. We show that TUT4(7) ZnF2 contains two distinct
RNA binding surfaces that are used in the interaction with different
RNA nucleobases in different targets, i.e that this small domain encodes diversity in TUT4(7) selectivity and molecular function. Interestingly and unlike other well-characterized CCHC ZnFs, ZnF2 is not physically coupled to the flanking ZnF3 and acts independently in
miRNA recognition, while the remaining CCHC ZnF of TUT4(7), ZnF1, has lost its intrinsic
RNA binding capability. Together, our data suggest that the ZnFs of TUT4(7) are independent units for
RNA and, possibly,
protein-
protein interactions that underlay the
protein's functional flexibility and are likely to play an important role in building its interaction network.