Determinants of microRNA processing inhibition by the developmentally regulated RNA-binding protein Lin28.
The developmentally regulated RNA-binding protein Lin28 blocks processing of let-7 family microRNAs (miRNAs) in embryonic cells. The molecular basis for this selective miRNA processing block is unknown. Here we find that Lin28 selectively binds the terminal loop region of let-7 precursors in vitro and that the loop mediates miRNA processing inhibition in vivo. Additionally, we identify the domains of Lin28 required for this inhibition. These findings establish a regulatory role for the terminal loop of precursors in miRNA maturation and provide insight into the mechanism by which Lin28 negatively regulates let-7 processing.
Stem Cell Program, Children's Hospital Boston, the Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Elena
E
Piskounova
Srinivas R
SR
Viswanathan
Maja
M
Janas
Robert J
RJ
LaPierre
George Q
GQ
Daley
Piotr
P
Sliz
Richard I
RI
Gregory
D001483:Base Sequence; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000737:chemistry*; D012689:Sequence Homology, Nucleic Acid
C000715187:Lin28A protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C487931:mirnlet7 microRNA, human