3′ Uridylation and the regulation of RNA function in the cytoplasm

Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Biochemical Society Transactions (Impact Factor: 3.19). 08/2010; 38(4):1150-3. DOI: 10.1042/BST0381150
Source: PubMed


Degradation of cytoplasmic mRNAs is an important aspect of the regulation of gene function in eukaryotes. Much of what is currently known about the underlying pathways of mRNA decay is derived from studies of the budding yeast Saccharomyces cerevisiae, in which mRNA turnover is initiated by deadenylation, followed either by decapping and 5'-->3' degradation or by further 3'-->5' exonucleolysis. Our studies using RNA cRACE (circularization-based rapid amplification of cDNA ends) techniques indicate that mRNA decapping in the fission yeast Schizosaccharomyces pombe often does not require prior deadenylation. Furthermore, the poly(A) polymerase-related, cytoplasmic enzyme Cid1 catalyses uridylation of a variety of functionally diverse poly(A)(+) mRNAs and hence stimulates decapping as part of a novel mRNA turnover pathway. The pathways initiated by uridylation and deadenylation stimulate decapping in a partially redundant fashion, but urg1 mRNA is stabilized in mutants lacking cid1. Accumulation of uridylated RNAs in an lsm1 mutant suggests an involvement of the Lsm1-7 complex in recognition of the 3' uridylation tag and recruitment of the decapping machinery. Recent reports from other groups suggest that in metazoans, which unlike budding yeast contain Cid1 orthologues, 3' uridylation by such enzymes is used to regulate miRNA (microRNA) and siRNA (small interfering RNA) biogenesis and activity. It has further been suggested that uridylation is an important regulatory modification of non-polyadenylated replication-dependent histone mRNAs. This modification may also form the basis of a widespread mechanism for the initiation of the decay of polyadenylated mRNAs in organisms other than fission yeast.

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    • "We cannot rule out that misprocessed rRNAs accumulating in rrp6l2 mutants are exported from the nucleus and recognized as aberrant RNAs by the cytosolic uridylation machinery to target these RNA substrates to degradation by SOV. In fact, RNA uridylation can – depending on the organism, the nature of the target RNA, and proteins that are recruited to uridylated transcripts – either protect from 3' exoribonucleolytic attacks, promote RNA degradation or favor processing (Mullen and Marzluff, 2008; Rissland and Norbury, 2009; Lehrbach et al., 2009; Norbury, 2010; Ibrahim et al., 2010; Zhao et al., 2012; Ren et al., 2012; Sement et al., 2013; Lim et al., 2014). Whether and how uridylation affects the fate of rRNA precursors, and whether uridylation is actually required for ribosome biogenesis in humans and plants remains to be resolved. "
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    • "Lsm1-7 complex also binds certain viral mRNAs with a 5′ poly(A) tract, thereby stabilizing these mRNAs by inhibiting both 3′-5′ and 5′-3′ decay28. Besides its role in general mRNA decay, Lsm1-7 complex is also involved in histone mRNA decay15,29, uridylation-mediated mRNA decapping11,30 and microRNA (miRNA) biogenesis31,32,33,34,35 by recognizing and binding to the 3′ poly(U) tract of the target RNAs in these processes. "
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    Full-text · Article · Nov 2013 · Cell Research
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    • "Uridylation participates in the control of RNA stability in various eukaryotes, from Schizosaccharomyces pombe to nematodes, plants or man. The broad spectrum of RNAs subjected to uridylation includes U6 snRNA, mRNAs, RNA-induced silencing complex (RISC)-cleaved fragments, small RNAs and their precursors (1–5). Uridylation has diverse effects on the fate of non-coding RNAs. "
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    ABSTRACT: Degradation of mRNAs is usually initiated by deadenylation, the shortening of long poly(A) tails to oligo(A) tails of 12–15 As. Deadenylation leads to decapping and to subsequent 5′ to 3′ degradation by XRN proteins, or alternatively 3′ to 5′ degradation by the exosome. Decapping can also be induced by uridylation as shown for the non-polyadenylated histone mRNAs in humans and for several mRNAs in Schizosaccharomyces pombe and Aspergillus nidulans. Here we report a novel role for uridylation in preventing 3′ trimming of oligoadenylated mRNAs in Arabidopsis. We show that oligo(A)-tailed mRNAs are uridylated by the cytosolic UTP:RNA uridylyltransferase URT1 and that URT1 has no major impact on mRNA degradation rates. However, in absence of uridylation, oligo(A) tails are trimmed, indicating that uridylation protects oligoadenylated mRNAs from 3′ ribonucleolytic attacks. This conclusion is further supported by an increase in 3′ truncated transcripts detected in urt1 mutants. We propose that preventing 3′ trimming of oligo(A)-tailed mRNAs by uridylation participates in establishing the 5′ to 3′ directionality of mRNA degradation. Importantly, uridylation prevents 3′ shortening of mRNAs associated with polysomes, suggesting that a key biological function of uridylation is to confer 5′ to 3′ polarity in case of co-translational mRNA decay.
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