Regulated dicing of pre-mir-144 via reshaping of its terminal loop

Although the route to generate microRNAs (miRNAs) is often depicted as a linear series of sequential and constitutive cleavages, we now appreciate multiple alternative pathways as well as diverse strategies to modulate their processing and function. Here, we identify an unusually profound regulatory role of conserved loop sequences in vertebrate pre-mir-144, which are essential for its cleavage by the Dicer RNase III enzyme in human and zebrafish models. Our data indicate that pre-mir-144 dicing is positively regulated via its terminal loop, and involves the ILF3 complex (NF90 and its partner NF45/ILF2). We provide further evidence that this regulatory switch involves reshaping of the pre-mir-144 apical loop into a structure that is appropriate for Dicer cleavage. In light of our recent findings that mir-144 promotes the nuclear biogenesis of its neighbor mir-451, these data extend the complex hierarchy of nuclear and cytoplasmic regulatory events that can control the maturation of clustered miRNAs.

Automated summary

A study has revealed the important regulatory role of conserved loop sequences in the generation of miRNAs in vertebrates, particularly in the cleavage of pre-mir-144. This regulatory role involves the ILF3 complex and reshaping of the apical loop of pre-mir-144, allowing for cleavage by Dicer. Furthermore, these findings extend our understanding of nuclear and cytoplasmic regulatory events in miRNA maturation.