The role of 3' end uridylation in RNA metabolism and cellular physiology

Abstract

Most eukaryotic RNAs are posttranscriptionally modified. The majority of modifications promote RNA maturation, others may regulate function and stability. The 3' terminal non-templated oligouridylation is a widespread modification affecting many cellular RNAs at some stage of their life cycle. It has diverse roles in RNA metabolism. The most prevalent is the regulation of stability and quality control. On the cellular and organismal level, it plays a critical role in a number of pathways, such as cell cycle regulation, cell death, development or viral infection. Defects in uridylation have been linked to several diseases. This review summarizes the current knowledge about the role of the 3' terminal oligo(U)-tailing in biology of various RNAs in eukaryotes and describes key factors involved in these pathways.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.

Keywords: RNA degradation; RNA modification; RNA processing; RNA surveillance; RNA uridylation; tutase.

Figure 1.

The role of 3′ uridylation in mRNA metabolism. (a) Uridylation of polyadenylated mRNAs, (i) the upstream cleavage mRNA 5′ fragments resulting from miRNA-directed mRNA cleavage are uridylated, decapped and degraded from 5′ and 3′ termini by exonuclease XRN1 and DIS3L2, respectively. The 5′ terminal mRNA fragments (5′mRFs) are uridylated and chopped in the 3′–5′ direction by RICE1/2 in Arabidopsis, and DIS3L2 in mammals. (ii) In S. pombe, uridylation of mRNA with naturally short poly(A)-tails promotes binding of the Lsm1–7 complex, which triggers decapping by DCP1/2 and mRNA is then degraded in the 5′–3′ direction by XRN1 or in 3′–5′ direction by exosome and DIS3L2. (iii) In mammals, mRNAs with shortened poly(A)-tails are uridylated by TUT4/7, which triggers decapping and degradation in 5′–3′ direction by XRN1 and by exosome and DIS3L2 in 3′–5′ direction. CDS, coding sequence; UTR, untranslated region; Gppp, 5'guanosine-triphosphate cap. (b) Uridylation of histone mRNAs has opposing roles. (i) During S-phase of the cell cycle, when histone mRNAs are trimmed by 3′hExo, they are stabilized via addition of 1–2 Us. (ii) At the end of S-phase of the cell cycle histone mRNAs are partially trimmed by 3′hExo, uridylated by TUT7 and upon decapping degraded in 5′–3′ direction by XRN1 and the exosome in 3′–5′ direction.

Figure 2.

The role of 3′ uridylation in metabolism of ncRNAs. (a) Uridylation in biogenesis of let-7 miRNA (i) Group II let-7 miRNAs are monouridylated by TUT4/7, which promotes processing by Dicer, and of U6 snRNA (ii) TENT1 uridylates precursors of U6 snRNA, exonuclease USB1 trims oligo(U)-tails down to 4 Us and leaves the terminal U with 2′, 3′cyclic phosphate. (b) Uridylation in snRNA decay. (i) mature short RNAs can be monouridylated by TUTases and degraded in 3′–5′ direction by exosome and/or DIS3L2. In Arabidopsis, SDN1/2 first removes 2′–O-methylation, then TUTase HESO1 adds oligo(U)-tail and small RNAs (sRNAs) are degraded by yet unknown 3′–5′ exonuclease. (ii) TDS mediates surveillance of various highly structured aberrant ncRNAs in the cytoplasm.