RNA-specific ribonucleotidyl transferases

Martín, Georges; Keller, Walter

doi:10.1261/rna.652807

Cited by 186 publications

(236 citation statements)

References 119 publications

(172 reference statements)

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“…Furthermore, the exosome's reported lack of phosphorolytic activity and "inconvenient" IMS localization of hPNPase agree with their lack of involvement. Possible candidates, especially for producing the observed A/U-rich heteropolymeric tails, could be among the seven noncanonical poly(A) polymerases recently identified in human cells, as nc-PAPs have been shown to add either As or Us (28,40,41). However, many of the isolated heteropolymeric sequences are A/G-rich and could possibly be produced by a different factor.…”

Section: Why Did Silencing Of Hxrn1 Results In the Accumulation Of Trumentioning

confidence: 99%

Addition of poly(A) and poly(A)-rich tails during RNA degradation in the cytoplasm of human cells

Slomovic

Fremder

Staals

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Polyadenylation of RNA is a posttranscriptional modification that can play two somewhat opposite roles: stable polyadenylation of RNA encoded in the nuclear genomes of eukaryote cells contributes to nuclear export, translation initiation, and possibly transcript longevity as well. Conversely, transient polyadenylation targets RNA molecules to rapid exonucleolytic degradation. The latter role has been shown to take place in prokaryotes and organelles, as well as the nucleus of eukaryotic cells. Here we present evidence of hetero-and homopolymeric adenylation of truncated RNA molecules within the cytoplasm of human cells. RNAi-mediated silencing of the major RNA decay machinery of the cell resulted in the accumulation of these polyadenylated RNA fragments, indicating that they are degradation intermediates. Together, these results suggest that a mechanism of RNA decay, involving transient polyadenylation, is present in the cytoplasm of human cells.exosome | heteropolymeric tails | RNA polyadenylation R NA polyadenylation occurs throughout the biological world.Stable poly(A) is associated with the mature 3′ end of most mRNAs encoded in the nuclear genome of eukaryotes. It is important for nuclear export and efficient translation initiation and may also contribute to transcript longevity (1). In turn, mRNA degradation in the cytoplasm usually initiates with deadenylation of the stable poly(A) tail, followed by either further degradation of the mRNA body by the exosome (3′-5′ pathway) or removal of the 5′ cap and subsequent 5′-3′ degradation by hXrn1 (exoribonuclease 1; 5′-3′ pathway) (2-4).Unlike stable poly(A), transient poly(A) is not associated with the mature 3′ end of the transcript. RNA decay pathways that use transient poly(A) include a stage in which poly(A) or poly (A)-rich tails are added to the 3′ ends of truncated degradation intermediates and are believed to assist exoribonucleases in their rapid degradation. As the tail addition can occur after endonucleolytic cleavage of the RNA or repetitive adenylation and 3′-5′ digestion, it often appears to be at "internal" positions relative to the full RNA sequence (5, 6). The term "transient" is used because the short-lived tail is degraded along with the RNA fragment. Transient poly(A) was first disclosed in Escherichia coli and then in additional bacteria, organelles, archaea and, eventually, in yeast and human nuclei (4,5,(7)(8)(9). In all systems in which truncated, polyadenylated RNA fragments were initially detected, they were later found to be correlated to poly(A)-assisted RNA decay (4,7,8).In yeast nuclei, transient poly(A) was found to play a role in RNA quality control wherein polyadenylation, initiated by the TRAMP complex, targets incorrectly folded tRNA molecules to degradation by the nuclear exosome (10, 11). In human cells, cotranscriptionally cleaved 3′ regions of an introduced β-globin gene and a class of short, highly unstable RNAs, dubbed PROMPTs (promoter upstream transcripts), were found to be adenylated and accumulated when the exosome wa...

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Section: Why Did Silencing Of Hxrn1 Results In the Accumulation Of Trumentioning

confidence: 99%

Addition of poly(A) and poly(A)-rich tails during RNA degradation in the cytoplasm of human cells

Slomovic

Fremder

Staals

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…In human, several small ncRNAs, such as 7SL(SRP), 7SK, U2, U6, and 5S RNAs, are post-transcriptionally uridylated or adenylated at their 39 termini (Perumal and Reddy 2002). A family of noncanonical poly(A) polymerases might be involved in such 39-terminal adenylation/uridylation of ncRNAs and some deadenylated mRNAs (Kwak and Wickens 2007;Martin and Keller 2007;Rissland et al 2007). Uridylation and adenylation occur competitively, and a single adenylation prevents further oligo-uridylation (Chen et al 2000).…”

mentioning

confidence: 99%

Selective stabilization of mammalian microRNAs by 3′ adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2

Katoh¹,

Sakaguchi²,

Miyauchi³

et al. 2009

Genes Dev.

398

395

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The steady-state levels of microRNAs (miRNAs) and their activities are regulated by the post-transcriptional processes. It is known that 39 ends of several miRNAs undergo post-dicing adenylation or uridylation. We isolated the liver-specific miR-122 from human hepatocytes and mouse livers. Direct analysis by mass spectrometry revealed that one variant of miR-122 has a 39-terminal adenosine that is introduced after processing by Dicer. We identified GLD-2, which is a regulatory cytoplasmic poly(A) polymerase, as responsible for the 39-terminal adenylation of miR-122 after unwinding of the miR-122/ miR-122* duplex. In livers from GLD-2-null mice, the steady-state level of the mature form of miR-122 was specifically lower than in heterozygous mice, whereas no reduction of pre-miR-122 was observed, demonstrating that 39-terminal adenylation by GLD-2 is required for the selective stabilization of miR-122 in the liver.Supplemental material is available at http://www.genesdev.org.

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“…Trf4p/5p belongs to a family of ribonucleotide transferases in the Pol ß superfamily of nucleotidyl transferases (10,11). It consists of N-and C-terminal sequences that have little predicted secondary structure, a catalytic domain similar in sequence to several Pol ß members with known structures, and an adjacent "central domain," which shares a short nucleotide recognition motif hx(I/L/V)(E/Q)(E/D/N)PhxxxxNxx (h, hydrophobic; x, any residue) with so-called noncanonical Pol β RNA polymerases.…”

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confidence: 99%

Structure and function of the polymerase core of TRAMP, a RNA surveillance complex

Hamill¹,

Wolin

Reinisch³

2010

Proc. Natl. Acad. Sci. U.S.A.

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The Trf4p/Air2p/Mtr4p polyadenylation (TRAMP) complex recognizes aberrant RNAs in Saccharomyces cerevisiae and targets them for degradation. A TRAMP subcomplex consisting of a noncanonical poly(A) RNA polymerase in the Pol ß superfamily of nucleotidyl transferases, Trf4p, and a zinc knuckle protein, Air2p, mediates initial substrate recognition. Trf4p and related eukaryotic poly(A) and poly(U) polymerases differ from other characterized enzymes in the Pol ß superfamily both in sequence and in the lack of recognizable nucleic acid binding motifs. Here we report, at 2.7-Å resolution, the structure of Trf4p in complex with a fragment of Air2p comprising two zinc knuckle motifs. Trf4p consists of a catalytic and central domain similar in fold to those of other noncanonical Pol β RNA polymerases, and the two zinc knuckle motifs of Air2p interact with the Trf4p central domain. The interaction surface on Trf4p is highly conserved across eukaryotes, providing evidence that the Trf4p/Air2p complex is conserved in higher eukaryotes as well as in yeast and that the TRAMP complex may also function in RNA surveillance in higher eukaryotes. We show that Air2p, and in particular sequences encompassing a zinc knuckle motif near its N terminus, modulate Trf4p activity, and we present data supporting a role for this zinc knuckle in RNA binding. Finally, we show that the RNA 3′ end plays a role in substrate recognition.protein-RNA interactions | RNA quality control T he vast majority of transcripts from eukaryotic genomes do not encode proteins. These transcripts include precursors to noncoding RNAs, such as transfer and ribosomal RNAs, small nuclear and nucleolar RNAs, microRNAs, siRNAs, and piRNAs. These noncoding RNAs often fold into intricate three-dimensional structures that are critical for subsequent processing and for assembling with proteins to form ribonucleoprotein complexes. In addition, genomic sequencing experiments in both yeast and mammals have revealed the existence of a large number of short-lived noncoding transcripts that initiate near RNA polymerase II promoters.

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RNA-specific ribonucleotidyl transferases

Cited by 186 publications

References 119 publications

Addition of poly(A) and poly(A)-rich tails during RNA degradation in the cytoplasm of human cells

Addition of poly(A) and poly(A)-rich tails during RNA degradation in the cytoplasm of human cells

Selective stabilization of mammalian microRNAs by 3′ adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2

Structure and function of the polymerase core of TRAMP, a RNA surveillance complex

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