News item

“Tailor” shapes the miRNA repertoire in Drosophila

Madalena Reimão-Pinto and her colleagues in Stefan Ameres’ Lab at IMBA report today in Molecular Cell the identification of a new enzyme – “Tailor”. Tailor is a small RNA uridylyltransferase in Drosophila, which adds short uridine tails to pre-miRNAs, thus regulating miRNA maturation. Namely, its action prevents the maturation of an entire class of non-canonical miRNAs – mirtrons - and therefore inhibits the de novo creation of miRNAs.

The name Tailor (as in the profession of making tailor-fitted suits) was chosen because this protein shapes, i.e., tailors, the miRNA repertoire in the cell. In the image you see sewing of a U-Tail (in red) into a RNA hairpin (black stitches)

Madalena and colleagues show how miRNA post-transcriptional modifications, although infrequent, have a broad impact on the miRNA population and its regulatory potential. This is Madalena’s first paper from her PhD at the Vienna Biocenter, for which Madalena was awarded a BI Fonds Fellowship.

“The cool thing about this paper is the fact that we look systematically at all miRNAs in an unbiased way. From this unbiased approach - looking in cell lines and flies - we hypothesized that Tailor mediates uridylation of pre-miRNAs, consequently regulating the abundance of mature miRNAs. We also noticed that it preferentially acted on a particular class of pre-miRNAs, suggesting that Tailor could distinguish between different classes, but it was unclear to us how this specificity was achieved. To test our hypothesis we established a high-throughput biochemical “in vitro” assay. This assay not only supported our hypothesis, but the results also allowed us to understand how Tailor distinguishes its substrates. We then went back to the “in vivo” data and confirmed that indeed there is substrate specificity – something that we had overlooked before.” Madalena M. Reimão-Pinto

This is another paper where we can easily see how technology advancements are crucial in science. Next Generation Sequencing was a fundamental tool in this story, and of course Madalena and her colleagues acknowledge the fact that having a sequencing facility “in-house”, run by an excellent team, makes a huge difference (NGS at CSF).  Madalena also told me that she had a lot of fun going from the data to the figures, trying out different ways to visualize their data in a meaningful way:

“you must have defined questions you want to answer when you start your analysis, otherwise you get lost in all the sequencing data.” Madalena M. Reimão-Pinto

I encourage you all to read the paper and we look forward to more developments in the Tailor story.

Well done Madalena!

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Reimão-Pinto MM, Ignatova V, Burkard TR, Hung J-H, Manzenreither RA, Sowemimo I, Herzog VA, Reichholf B, Fariña-Lopez S and Ameres SL (2015) Uridylation of RNA Hairpins by Tailor Confines the Emergence of MicroRNAs in Drosophila. Molecular Cell doi.org/10.1016/j.molcel.2015.05.033 Link