Antagonistic role of hnRNP A1 and KSRP in the regulation of let-7a biogenesis

Nat Struct Mol Biol. 2010 Aug;17(8):1011-8. doi: 10.1038/nsmb.1874. Epub 2010 Jul 18.


The pluripotency-promoting proteins Lin28a and Lin28b act as post-transcriptional repressors of let-7 miRNA biogenesis in undifferentiated embryonic stem cells. The levels of mature let-7a differ substantially in cells lacking Lin28 expression, indicating the existence of additional mechanism(s) of post-transcriptional regulation. Here, we present evidence supporting a role for heteronuclear ribonucleoprotein A1 (hnRNP A1) as a negative regulator of let-7a. HnRNP A1 binds the conserved terminal loop of pri-let-7a-1 and inhibits its processing by Drosha. Levels of mature let-7a negatively correlate with hnRNP A1 levels in somatic cell lines. Furthermore, hnRNP A1 depletion increased pri-let-7a-1 processing by cell extracts, whereas its ectopic expression decreased let-7a production in vivo. Finally, hnRNP A1 binding to let-7a interferes with the binding of KSRP, which is known to promote let-7a biogenesis. We propose that hnRNP A1 and KSRP have antagonistic roles in the post-transcriptional regulation of let-7a expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding, Competitive
  • Cell Line, Tumor
  • DNA Footprinting
  • Gene Expression Regulation, Neoplastic
  • Green Fluorescent Proteins / metabolism
  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism*
  • Humans
  • MicroRNAs / biosynthesis*
  • MicroRNAs / chemistry
  • MicroRNAs / genetics
  • Models, Biological
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Protein Binding
  • RNA Processing, Post-Transcriptional
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Ribonuclease III / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*


  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • KHSRP protein, human
  • MicroRNAs
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Trans-Activators
  • mirnlet7 microRNA, human
  • Green Fluorescent Proteins
  • DROSHA protein, human
  • Ribonuclease III