Surprises in the 3′‐end: ‘U’ can decide too!

RNA molecules are subjected to post‐transcriptional modifications that might determine their maturation, activity, localization and stability. These alterations can occur within the RNA molecule or at its 5′‐ or 3′‐ extremities, and are essential for gene regulation and proper function of the RNA . One major type of modification is the 3′‐end addition of nontemplated nucleotides. Polyadenylation is the most well studied type of 3′‐ RNA modification, both in eukaryotes and prokaryotes. The importance of 3′‐oligouridylation has recently gained attention through the discovery of several types of uridylated‐ RNA s, by the existence of enzymes that specifically add poly(U) tails and others that preferentially degrade these tails. Namely, Dis3L2 is a 3′–5′ exoribonuclease from the RN ase  II / RNB family that has been shown to act preferentially on oligo(U)‐tailed transcripts. Our understanding of this process is still at the beginning, but it is already known to interfere in the regulation of diverse RNA species in most eukaryotes. Now that we are aware of the prevalence of RNA uridylation and the techniques available to globally evaluate the 3′‐terminome, we can expect to make rapid progress in determining the extent of terminal oligouridylation in different RNA populations and unravel its impact on RNA decay mechanisms. Here, we sum up what is known about 3′‐ RNA modification in the different cellular compartments of eukaryotic cells, the conserved enzymes that perform this 3′‐end modification and the effectors that are selectively activated by this process.