Posttranscriptional regulation of miRNAs harboring conserved terminal loops.
We recently found that hnRNP A1, a protein implicated in many aspects of RNA processing, acts as an auxiliary factor for the Drosha-mediated processing of a microRNA precursor, pri-miR-18a. Here, we provide the mechanism by which hnRNP A1 regulates this event. We show that hnRNP A1 binds to the loop of pri-miR-18a and induces a relaxation at the stem, creating a more favorable cleavage site for Drosha. We found that approximately 14% of all pri-miRNAs have highly conserved loops, which we predict act as landing pads for trans-acting factors influencing miRNA processing. In agreement, we show that 2'O-methyl oligonucleotides targeting conserved loops (LooptomiRs) abolish miRNA processing in vitro. Furthermore, we present evidence to support an essential role of conserved loops for pri-miRNA processing. Altogether, these data suggest the existence of auxiliary factors for the processing of specific miRNAs, revealing an additional level of complexity for the regulation of miRNA biogenesis.
Michlewski
Gracjan
G
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh EH4 2XU, UK.
Guil
Sonia
S
Semple
Colin A
CA
Cáceres
Javier F
JF
D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D018983:DNA Footprinting; D015894:Genome, Human; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D017393:RNA Editing; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D035683:MicroRNAs; D012333:RNA, Messenger