Stimulation of pri-miR-18a processing by hnRNP A1

Gracjan Michlewski, Sonia Guil, Javier F Cáceres

Research output: Contribution to journalArticlepeer-review


Recent evidence suggests that the canonical miRNA processing pathway can b regulated by a number of positive and negative trans-acting factors. This chapter provides an overview of hnRNP A1-mediated regulation of miR-18a biogenesis. Our laboratory has recently established that the multifunctional RNA-binding protein hnRNP A1 is required for the processing of miR-18a at the nuclear of Drosha-mediated processing. By combining structural and functional analysis of RNA, we showed that hnRNP A1 regulates the processing of pri-miR-18a by binding to its terminal loop and reshaping its stem-loop structure, thus allowing for a more effective Drosha cleavage. Furthermore, we linked the event of hnRNP A1-binding to the pri-miR-18a with an unusual phylogenetic sequence conservation of its terminal loop. Bioinformatic and mutational analysis revealed that a number of pri-miRNAs have highly conserved terminal loops, which are predicted to act as landing pads for trans-acting factors influencing miRNA processing. These results underscore a previously uncharacterized role for general RNA-binding proteins as factors that facilitate the processing of specific miRNAs, revealing an additional level of complexity for the regulation of miRNA production and function.
Original languageEnglish
Pages (from-to)28-35
Number of pages8
JournalAdvances in Experimental Medicine and Biology
Publication statusPublished - 2010


  • Animals
  • Base Sequence
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • Humans
  • MicroRNAs
  • Molecular Sequence Data
  • Ribonuclease III


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