It’s December, the time of year when much of the States is blanketed in a frosty mantle of the white stuff. But as recently reported in Molecular Cell, the ACA45 RNA appears to have pulled the ultimate snow job. Nikolaus Rajewsky, Gunter Meister, and colleagues revealed that ACA45, which was previously thought to function exclusively as a small nucleolar RNA (snoRNA), is also processed to a shorter sequence with miRNA-like functions. The work was conducted at the Max Planck Institutes of Biochemistry and of Molecular Genetics, the Max Delbrück Center for Molecular Medicine (all in Germany), New York University, and IBMP-CNRS (France).
The researchers made this discovery by analyzing small RNAs that associate with human Argonaute (Ago)1 and Ago2 proteins. Ago proteins bind to small ncRNAs to form gene silencing effector complexes. By immunoprecipitating Ago1 and Ago2 and deep sequencing the associated small RNAs, the investigators identified small RNAs that originated from ACA45. snoRNAs such as ACA45 function in the maturation of ribosomal RNAs or small nuclear RNAs by guiding chemical modifications.
In human cells, a small portion of the total ACA45 snoRNA was exported from the nucleus and processed by Dicer to 20-25-nt RNAs, which associated with Ago1 and Ago2. miRNA target prediction algorithms and luciferase reporter assays revealed that the CDC2L6 subunit of the mediator transcriptional coactivator complex is a potential target of ACA45 miRNA-like activity. Furthermore, the researchers identified other human snoRNAs with miRNA-like processing signatures. Grab a cup of hot chocolate and read all the chilling details at Molecular Cell, December 2008.