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

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.