The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a

Nat Struct Mol Biol. 2007 Jul;14(7):591-6. doi: 10.1038/nsmb1250. Epub 2007 Jun 10.


hnRNP A1 is an RNA-binding protein involved in various aspects of RNA processing. Use of an in vivo cross-linking and immunoprecipitation protocol to find hnRNP A1 RNA targets resulted in the identification of a microRNA (miRNA) precursor, pre-miR-18a. This microRNA is expressed as part of a cluster of intronic RNAs, including miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1 and miR-92, and potentially acts as an oncogene. Here we show that hnRNP A1 binds specifically to the primary RNA sequence pri-miR-18a before Drosha processing. HeLa cells depleted of hnRNP A1 have reduced in vitro processing activity with pri-miR-18a and also show reduced abundances of endogenous pre-miR-18a. Furthermore, we show that hnRNP A1 is required for miR-18a-mediated repression of a target reporter in vivo. These results underscore a previously uncharacterized role for general RNA-binding proteins as auxiliary factors that facilitate the processing of specific miRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation*
  • HeLa Cells
  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / chemistry
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism*
  • Humans
  • MicroRNAs / chemistry
  • MicroRNAs / metabolism*
  • RNA Precursors / metabolism
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Ribonuclease III / metabolism


  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • MIRN18A microRNA, human
  • MicroRNAs
  • RNA Precursors
  • RNA-Binding Proteins
  • DROSHA protein, human
  • Ribonuclease III