Importance of the NCp7-like domain in the recognition of pre-let-7g by the pluripotency factor Lin28

Nucleic Acids Res. 2012 Feb;40(4):1767-77. doi: 10.1093/nar/gkr808. Epub 2011 Oct 19.


The pluripotency factor Lin28 is a highly conserved protein comprising a unique combination of RNA-binding motifs, an N-terminal cold-shock domain and a C-terminal region containing two retroviral-type CCHC zinc-binding domains. An important function of Lin28 is to inhibit the biogenesis of the let-7 family of microRNAs through a direct interaction with let-7 precursors. Here, we systematically characterize the determinants of the interaction between Lin28 and pre-let-7 g by investigating the effect of protein and RNA mutations on in vitro binding. We determine that Lin28 binds with high affinity to the extended loop of pre-let-7 g and that its C-terminal domain contributes predominantly to the affinity of this interaction. We uncover remarkable similarities between this C-terminal domain and the NCp7 protein of HIV-1, not only in terms of primary structure but also in their modes of RNA binding. This NCp7-like domain of Lin28 recognizes a G-rich bulge within pre-let-7 g, which is adjacent to one of the Dicer cleavage sites. We hypothesize that the NCp7-like domain initiates RNA binding and partially unfolds the RNA. This partial unfolding would then enable multiple copies of Lin28 to bind the extended loop of pre-let-7 g and protect the RNA from cleavage by the pre-microRNA processing enzyme Dicer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Mice
  • MicroRNAs / chemistry*
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Precursors / chemistry*
  • RNA Precursors / metabolism
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / metabolism
  • gag Gene Products, Human Immunodeficiency Virus / chemistry


  • Lin-28 protein, mouse
  • MicroRNAs
  • NCP7 protein, Human immunodeficiency virus 1
  • RNA Precursors
  • RNA-Binding Proteins
  • gag Gene Products, Human Immunodeficiency Virus
  • mirnlet7 microRNA, mouse