Small silencing RNAs, such as microRNAs, play a key role in the regulation of gene expression at the post-transcriptional level. They have important functions in coordinating organismal development, physiological processes and human diseases, such as cancer. In a study published in the journal Molecular Cell today, researchers at the Institute of Molecular Biotechnology (IMBA) identify a new enzyme that marks precursor transcripts of microRNAs to regulate their maturation into gene regulatory small RNAs. “This is why we called the enzyme ‘Tailor’, because it reflects its ability to shape the repertoire of microRNAs”, says Madalena Ramão-Pinto, first author of the study, whose work is supported by the prestigious Boehringer Ingelheim fellowship.
The detailed molecular characterization of this enzyme revealed that it adds nucleotides (preferentially uridine) to the ends of RNA transcripts, which directly impacts not only further processing, but also the stability of these molecules. By this mechanism, Tailor dampens the ability of many transcripts to generate small RNAs, putting a threshold to the de novo generation of microRNAs. “In that sense, this is a nice example for how the systematic characterization of molecular signatures in small RNAs enable us to uncover remarkable failsafe mechanisms in post-transcriptional gene regulatory pathways with enormous biological and biomedical importance”, says Stefan Ameres, group leader at IMBA. This model is further supported by a second study, also co-authored by Stefan Ameres.
Together, these results support a new concept in which uridylating enzymes dictate the fate of RNA transcripts in order to shape gene expression profiles.
Original Publications
Madalena M. Reimão-Pinto, Valentina Ignatova, Thomas R. Burkard, Jui-Hung Hung, Raphael A. Manzenreither, Ivica Sowemimo, Veronika A. Herzog, Brian Reichholf, Sara Fariña-Lopez and Stefan L. Ameres (2015): Uridylation of RNA-hairpins by Tailor confines the emergence of MicroRNAs in Drosophila. Molecular Cell
doi:10.1016/j.molcel.2015.05.033
Diane Borolamiol-Becet, Fuqu Hu, David Jee, Jiayu Wen, Katsutomo Okamura, Ching-Jung Lin, Stefan L. Ameres and Eric C. Lai (2015): Selective Suppression of the Splicing-Mediated MicroRNA Pathway by the Terminal Uridyltransferase Tailor. Molecular Cell
doi:10.1016/j.molcel.2015.05.034