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

Abstract

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 0 -or 3 0 -extremities, and are essential for gene regulation and proper function of the RNA. One major type of modification is the 3 0 -end addition of nontemplated nucleotides. Polyadenylation is the most well studied type of 3 0 -RNA modification, both in eukaryotes and prokaryotes. The importance of 3 0 -oligouridylation has recently gained attention through the discovery of several types of uridylated-RNAs, by the existence of enzymes that specifically add poly(U) tails and others that preferentially degrade these tails. Namely, Dis3L2 is a 3 0 -5 0 exoribonuclease from the RNase 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 0 -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 0 -RNA modification in the different cellular compartments of eukaryotic cells, the conserved enzymes that perform this 3 0 -end modification and the effectors that are selectively activated by this process.

Biochemical and structural bioinformatics studies of fungal CutA nucleotidyltransferases explain their unusual specificity toward CTP and increased tendency for cytidine incorporation at the 3′-terminal positions of synthesized tails

“…mRNA uridylation and the responsible PUPs gained significant attention because they are conserved among eukaryotes (except Saccharomyces cerevisiae, which genome does not encode noncanonical NTase with PUP activity), although some species-specific differences exist (Scott and Norbury 2013;Munoz-Tello et al 2015;Viegas et al 2015;Scheer et al 2016). For instance, uridylation of oligo(A) tails in Arabidopsis thaliana by URT1 PUP does not seem to influence the mRNA degradation rates globally, but rather protects 3 ′ -ends from trimming to ensure a 5 ′ -3 ′ directionality of cotranslational mRNA decay (Sement et al 2013;Scheer et al 2016;Zuber et al 2016).…”

Lin28a uses distinct mechanisms of binding to RNA and affects miRNA levels positively and negatively

“…Polyuridylation ultimately results in pre-let-7 destabilization and a decrease of mature let-7 (Hagan et al 2009;Heo et al 2009). The degradation of poly(U) pre-let-7 is performed in the cytoplasm independently of the RNA exosome by 3 ′ -5 ′ Dis3l2 exoribonuclease from the RNase II/RNB family Ustianenko et al 2013), which has a preference for unstructured and poly(U)-rich RNAs Malecki et al 2013;Munoz-Tello et al 2015;Viegas et al 2015). Moreover, polyuridylation of pre-let-7 precludes Dicer from generating mature let-7 (Heo et al 2009).…”

Interrogating the degradation pathways of unstable mRNAs with XRN1-resistant sequences

“…16). Furthermore, transcripts with shortened poly(A) tails can be 3′-oligouridylated by TUTases, activating different degradation pathways including the 3′–5′ decay via the exosome-independent DIS3L2 (refs 17, 18, 19). …”