Polyadenylation and degradation of incomplete RNA polymerase I transcripts in mammalian cells

Shcherbik, Natalia; Wang, Minshi; Lapik, Yevgeniya R.; Srivastava, Leena; Pestov, Dimitri G.

doi:10.1038/embor.2009.271

Cited by 94 publications

(119 citation statements)

References 43 publications

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“…After ActD treatment, the 5'ETS was no longer detectable, as attributed to its degradation by ActD and lack of new rRNA synthesis, 42 while 28S rRNA signal increased by 2-fold in the nucleoli (Fig. 6D).…”

Section: Discussionmentioning

confidence: 99%

CRM1 and its ribosome export adaptor NMD3 localize to the nucleolus and affect rRNA synthesis

Bai

Moore

Laiho

2013

Nucleus

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Section: Discussionmentioning

confidence: 99%

CRM1 and its ribosome export adaptor NMD3 localize to the nucleolus and affect rRNA synthesis

Bai

Moore

Laiho

2013

Nucleus

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“…Identified substrates of TRAMP-dependent degradation or processing in yeast are so far restricted to nuclear RNAs. Similar mechanisms seem to operate in higher eukaryotes (West et al 2006;Shcherbik et al 2010;Lubas et al 2011;Berndt et al 2012). In mammalian cells, oligoadenylation of cytoplasmic mRNAs and rRNA fragments has been described.…”

Section: Introductionmentioning

confidence: 89%

Oligoadenylation of 3′ decay intermediates promotes cytoplasmic mRNA degradation in Drosophila cells

Harnisch

Cuzic-Feltens

Dohm

et al. 2016

RNA

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Post-transcriptional 3′ end addition of nucleotides is important in a variety of RNA decay pathways. We have examined the 3 ′ end addition of nucleotides during the decay of the Hsp70 mRNA and a corresponding reporter RNA in Drosophila S2 cells by conventional sequencing of cDNAs obtained after mRNA circularization and by deep sequencing of dedicated libraries enriched for 3 ′ decay intermediates along the length of the mRNA. Approximately 5%-10% of 3 ′ decay intermediates carried nonencoded oligo(A) tails with a mean length of 2-3 nucleotides. RNAi experiments showed that the oligoadenylated RNA fragments were intermediates of exosomal decay and the noncanonical poly(A) polymerase Trf4-1 was mainly responsible for A addition. A hot spot of A addition corresponded to an intermediate of 3′ decay that accumulated upon inhibition of decapping, and knockdown of Trf4-1 increased the abundance of this intermediate, suggesting that oligoadenylation facilitates 3 ′ decay. Oligoadenylated 3 ′ decay intermediates were found in the cytoplasmic fraction in association with ribosomes, and fluorescence microscopy revealed a cytoplasmic localization of Trf4-1. Thus, oligoadenylation enhances exosomal mRNA degradation in the cytoplasm.

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“…Because promoter upstream transcripts are polyadenylated and degraded in an exosome-dependent manner in human cells (20) and aberrant pre-rRNAs have been shown to be polyadenylated by the Trf4 orthologue, PAPD5, in mouse cells (60), it seems highly likely that a human TRAMP complex will act as an exosome cofactor in the processing/degradation of ncRNAs in human cells. Very recently, hZCCHC7 and hPAPD5 were identified in hMTR4 and hRRP6 precipitates and shown to interact with each other and play a role in the polyadenylation of pre-rRNAs (61), providing strong support for a human TRAMP complex containing ZCCHC7 and PAPD5 and also supporting the data presented here.…”

Section: Discussionmentioning

confidence: 99%

Air1 Zinc Knuckles 4 and 5 and a Conserved IWRXY Motif Are Critical for the Function and Integrity of the Trf4/5-Air1/2-Mtr4 Polyadenylation (TRAMP) RNA Quality Control Complex

Fasken

Leung

Banerjee

et al. 2011

Journal of Biological Chemistry

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In Saccharomyces cerevisiae, non-coding RNAs, including cryptic unstable transcripts (CUTs), are subject to degradation by the exosome. The Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) complex in S. cerevisiae is a nuclear exosome cofactor that recruits the exosome to degrade RNAs. Trf4/5 are poly(A) polymerases, Mtr4 is an RNA helicase, and Air1/2 are putative RNA-binding proteins that contain five CCHC zinc knuckles (ZnKs). One central question is how the TRAMP complex, especially the Air1/2 protein, recognizes its RNA substrates. To characterize the function of the Air1/2 protein, we used random mutagenesis of the AIR1/2 gene to identify residues critical for Air protein function. We identified air1-C178R and air2-C167R alleles encoding air1/2 mutant proteins with a substitution in the second cysteine of ZnK5. Mutagenesis of the second cysteine in AIR1/2 ZnK1-5 reveals that Air1/2 ZnK4 and -5 are critical for Air protein function in vivo. In addition, we find that the level of CUT, NEL025c, in air1 ZnK1-5 mutants is stabilized, particularly in air1 ZnK4, suggesting a role for Air1 ZnK4 in the degradation of CUTs. We also find that Air1/2 ZnK4 and -5 are critical for Trf4 interaction and that the Air1-Trf4 interaction and Air1 level are critical for TRAMP complex integrity. We identify a conserved IWRXY motif in the Air1 ZnK4-5 linker that is important for Trf4 interaction. We also find that hZC-CHC7, a putative human orthologue of Air1 that contains the IWRXY motif, localizes to the nucleolus in human cells and interacts with both mammalian Trf4 orthologues, PAPD5 and PAPD7 (PAP-associated domain containing 5 and 7), suggesting that hZCCHC7 is the Air component of a human TRAMP complex.Production of mature RNAs in eukaryotes requires a complex set of processing steps, including 5Ј-end capping, splicing, 3Ј-end cleavage, polyadenylation, nucleolytic cleavage/trimming, and base modifications, by numerous processing components. Incorrectly processed RNAs are rapidly degraded by RNA quality control machinery to prevent deleterious effects on the cell. Processing and degradation of multiple classes of RNA are performed by RNA endo/exoribonucleases that are recruited to their RNA substrates by specific protein cofactors. These nucleases and their cofactors are highly regulated and evolutionarily conserved.In Saccharomyces cerevisiae, non-coding RNAs (ncRNAs), 2 including precursors of rRNAs, snoRNAs, and snRNAs, are processed and/or degraded by the nuclear exosome, an evolutionarily conserved ringlike riboexonuclease complex containing two active 3Ј-5Ј-riboexonucleases, Rrp44/Dis3 and Rrp6 (1-8). Hypomodified initiator tRNAs (tRNA i Met ) from cells with an impaired tRNA methyltransferase and aberrant pre-mRNAs from cells with defective 3Ј-end processing, splicing, or nuclear export factors are also degraded by the nuclear exosome (9 -13). More recently, a novel class of small (250 -300-nucleotide) intergenic RNA polymerase II transcripts, termed cryptic unstable transcripts (CUTs), was discovered in cells that lack ...

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Polyadenylation and degradation of incomplete RNA polymerase I transcripts in mammalian cells

Cited by 94 publications

References 43 publications

CRM1 and its ribosome export adaptor NMD3 localize to the nucleolus and affect rRNA synthesis

CRM1 and its ribosome export adaptor NMD3 localize to the nucleolus and affect rRNA synthesis

Oligoadenylation of 3′ decay intermediates promotes cytoplasmic mRNA degradation in Drosophila cells

Air1 Zinc Knuckles 4 and 5 and a Conserved IWRXY Motif Are Critical for the Function and Integrity of the Trf4/5-Air1/2-Mtr4 Polyadenylation (TRAMP) RNA Quality Control Complex

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