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

Abstract

One contribution of 11 to a theme issue '5 0 and 3 0 modifications controlling RNA degradation'.Most eukaryotic RNAs are posttranscriptionally modified. The majority of modifications promote RNA maturation, others may regulate function and stability. The 3 0 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 0 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 0 and 3 0 modifications controlling RNA degradation'.

Terminal nucleotidyl transferases (TENTs) in mammalian RNA metabolism

“…Here we describe the major findings with each of the TUTases, the differential impact of uridylation on different RNA classes and the global role of uridylation in mammals, concluding with the newest findings. See also reviews in this issue by Zigackova and Vanacova [ 117 ] and De Almeida et al . [ 118 ] on uridylation in other organisms.…”

The TUTase URT1 connects decapping activators and prevents the accumulation of excessively deadenylated mRNAs to avoid siRNA biogenesis

“…Uridylation targets most classes of eukaryotic RNAs, from small and large noncoding RNAs (ncRNAs) to mRNAs 1 – 3 . Uridylation of ncRNAs can promote maturation, control stability, or abrogate activity, depending on the type of ncRNAs and its cellular context 2 – 4 . For mRNAs, the prevalent role of uridylation is to trigger 5′-3′ and 3′-5′ degradation 5 – 8 .…”

mRNA Metabolism in Cardiac Development and Disease: Life After Transcription

“…Despite a broad impact on mRNA metabolism, many of the molecular details involving m6A-dependent regulation of RNA remain unknown ( 29 ). On the other hand, uridylation at the 3′-tail of mRNA is another form of post-transcriptional modification that is carried out by a family of terminal uridylyl transferases (TUTases) ( 36 , 119 , 247 ). The consensus is that adding the uridylation to polyadenylated mRNAs promotes exonuclease digestion of stalled RNA molecules; thus this type of modification effectively leads to “gene silencing” by targeted degradation of the mRNA ( 36 , 49 , 143 , 151 , 247 ).…”

“…Although much of the core machinery involved in the modification, splicing, and degradation of RNA are highly conserved, each step of these post-transcriptional processes can be modulated by developmental cues, cellular signaling, or environmental conditions in a cell type- and tissue-specific manner, and this is accomplished by a large number of RNA binding proteins ( 22 , 33 , 42 ). Furthermore, post-transcriptional modifications and editing are emerging as additional reprogramming signals that can potentially affect the functionality of RNA molecules ( 15 , 55 , 63 , 139 , 210 , 247 ). Consequently, a majority of protein coding genes in humans can produce multiple mRNA species encoding different protein products with potentially different regulatory properties that alter their intracellular localization, translational capacities, and turnover rates ( FIGURE 1 ).…”