Human helicase geneSKI2Win the HLA class III region exhibits striking structural similarities to the yeast antiviral geneSKI2and to the human geneKIAA0052:emergence of a new gene family

Dangel, Andrew W.; Shen, Like; Mendoza, Anna R.; Wu, Lai-Chu; Yu, Chack‐Yung

doi:10.1093/nar/23.12.2120

Cited by 61 publications

(45 citation statements)

References 48 publications

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“…However, putative RNA helicases and other cofactors that may target the exosome complex to its substrates have been identified. Several of the proteins required for these mRNA decay mechanisms have homologues in other eukaryotic cells, including mammals (Dangel et al, 1995;Lee et al, 1995;Bashkirov et al, 1997;Mitchell et al, 1997).…”

Section: Yeast Ski Complexmentioning

confidence: 99%

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

Bevilacqua

Ceriani

Capaccioli

et al. 2003

Journal Cellular Physiology

294

259

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Recent evidence suggests that gene expression may be regulated, at least in part, at post-transcriptional level by factors inducing the extremely rapid degradation of messenger RNAs. These factors include reactions between adenyl-uridyl-rich elements (AREs) of the relevant mRNA and either specific proteins that bind to these elements or exosomes. This review deals with examples of the proteins (AU-rich binding proteins, AUBPs) and exosomes, which have been shown to form complexes with AREs and bring about rapid degradation of the relevant mRNA, and with certain other factors, which protect the RNA from such degradation. The biochemical and physiological factors underlying the stability of messenger RNAs carrying the ARE motifs will be reviewed in the light of their emerging significance for cell physiology, human pathology, and molecular medicine. We also consider the possible application of the results of recent insights into the mechanisms to pharmacological interventions to prevent or cure disorders, especially developmental disorders, which the suppression of gene expression may bring about. Molecular targeting of specific steps in protein degradation by synthetic compounds has already been utilized for the development of pharmacological therapies.

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Section: Yeast Ski Complexmentioning

confidence: 99%

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

Bevilacqua

Ceriani

Capaccioli

et al. 2003

Journal Cellular Physiology

294

259

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“…Ski2p, Ski3p, and Ski8p are found in a cytoplasmic complex (4), but their precise role is unclear. As in yeast, there are two human Ski2p homologues (8,19,24,30).…”

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confidence: 99%

Linking the 3′ Poly(A) Tail to the Subunit Joining Step of Translation Initiation: Relations of Pab1p, Eukaryotic Translation Initiation Factor 5B (Fun12p), and Ski2p-Slh1p

Searfoss

Dever

Wickner

2001

Molecular and Cellular Biology

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The 3 poly(A) structure improves translation of a eukaryotic mRNA by 50-fold in vivo. This enhancement has been suggested to be due to an interaction of the poly(A) binding protein, Pab1p, with eukaryotic translation initiation factor 4G (eIF4G). However, we find that mutation of eIF4G eliminating its interaction with Pab1p does not diminish the preference for poly(A) ؉ mRNA in vivo, indicating another role for poly(A). We show that either the absence of Fun12p (eIF5B), or a defect in eIF5, proteins involved in 60S ribosomal subunit joining, specifically reduces the translation of poly(A) ؉ mRNA, suggesting that poly(A) may have a role in promoting the joining step. Deletion of two nonessential putative RNA helicases (genes SKI2 and SLH1) makes poly(A) dispensable for translation. However, in the absence of Fun12p, eliminating Ski2p and Slh1p shows little enhancement of expression of non-poly(A) mRNA. This suggests that Ski2p and Slh1p block translation of non-poly(A) mRNA by an effect on Fun12p, possibly by affecting 60S subunit joining.The 5Ј cap (7-methyl-GpppG. . .) and 3Ј poly(A) structures of eukaryotic mRNAs are both critically important for translation, for mRNA transport from the nucleus, and for mRNA stability in both the nucleus and the cytoplasm. The in vivo requirement for translation for the 3Ј poly(A) structure, estimated by electroporation of mRNAs into living cells, is about 50-fold, while that for the 5Ј cap is about 20-fold (11, 12).The effects of the 5Ј cap on translation are mediated by the cap-binding protein, eukaryotic translation initiation factor 4E (eIF4E) (Cdc33p), which associates with eIF4G in the eIF4F complex to promote binding of the mRNA to the 40S ribosomal subunit (through eIF3). A 43S preinitiation complex consisting of the 40S subunit, eIF3, and eIF2-GTP-MettRNA iMet is thought to bind to an mRNA mediated by interaction between eIF3 and eIF4G. This complex scans from the cap at the 5Ј end of the mRNA to the first AUG. There, with the help of eIF5 (Tif5p) and eIF5B (Fun12p), 60S subunit joining occurs and translation begins (27; reviewed in references 9 and 37). 60S subunit joining requires both eIF5 and eIF5B. While eIF5 promotes GTP hydrolysis by eIF2, enabling release of the initiation factors from the 40S subunit, eIF5B has its own GTP binding activity and hydrolyzes GTP in a ribosome-dependent reaction (27).The role of the 3Ј poly(A) structure in mRNA translation is not yet completely clear. The poly(A) binding protein (Pab1p) is believed to mediate many of the effects of the 3Ј poly(A) structure (reviewed in reference 34). Because the poly(A) tail apparently has roles in nuclear processes as well as cytoplasmic events (22), dissecting these mechanisms is difficult. The PAB1 gene is essential, indicating that at least one of the functions of Pab1p is critical to the cell.

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“…We have named this gene RAI1 for Rat1p interacting protein 1. This protein is conserved throughout eukaryotes, and its human homolog is DOM3Z (43), the gene for which maps adjacent to the human homolog of yeast SKI2 (11), encoding a putative RNA helicase required for 3Ј-mRNA degradation and repression of translation of poly(A)…”

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confidence: 99%

Saccharomyces cerevisiae RAI1 (YGL246c) Is Homologous to Human DOM3Z and Encodes a Protein That Binds the Nuclear Exoribonuclease Rat1p

Yang

Bai

Lee

et al. 2000

Molecular and Cellular Biology

109

115

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The RAT1 gene of Saccharomyces cerevisiae encodes a 533 exoribonuclease which plays an essential role in yeast RNA degradation and/or processing in the nucleus. We have cloned a previously uncharacterized gene (YGL246c) that we refer to as RAI1 (Rat1p interacting protein 1). RAI1 is homologous to Caenorhabditis elegans DOM-3 and human DOM3Z. Deletion of RAI1 confers a growth defect which can be complemented by an additional copy of RAT1 on a centromeric vector or by directing Xrn1p, the cytoplasmic homolog of Rat1p, to the nucleus through the addition of a nuclear targeting sequence. Deletion of RAI1 is synthetically lethal with the rat1-1 ts mutation and shows genetic interaction with a deletion of SKI2 but not XRN1. Polysome analysis of an rai1 deletion mutant indicated a defect in 60S biogenesis which was nearly fully reversed by high-copy RAT1. Northern blot analysis of rRNAs revealed that rai1 is required for normal 5.8S processing. In the absence of RAI1, 5.8S L was the predominant form of 5.8S and there was an accumulation of 3-extended forms but not 5-extended species of 5.8S. In addition, a 27S pre-rRNA species accumulated in the rai1 mutant. Thus, deletion of RAI1 affects both 5 and 3 processing reactions of 5.8S rRNA. Consistent with the in vivo data suggesting that RAI1 enhances RAT1 function, purified Rai1p stabilized the in vitro exoribonuclease activity of Rat1p.In the yeast Saccharomyces cerevisiae, two 5Ј33Ј exoribonucleases, Rat1p and Xrn1p (23,35), are functionally interchangeable and are localized to the nucleus and cytoplasm, respectively (19). These enzymes are conserved throughout eukaryotes but are apparently absent from prokaryotic cells based on analysis of protein sequences predicted from prokaryotic genomes. The mammalian counterparts of Rat1p and Xrn1p function in yeast and complement their respective mutants (8,33,34). These exoribonucleases processively degrade RNA containing a 5Ј-monophosphate (37, 38). RNA molecules with 7mG cap, 5Ј-triphosphate, or 5Ј-hydroxyl are resistant to degradation by these enzymes (38). The role of Xrn1p in general deadenylation-dependent mRNA degradation and in nonsense-mediated degradation is well established (18,26,27). Xrn1p also degrades the 5Ј fragment of internal transcribed spacer 1, resulting from cleavage at sites D and A 2 (36; reviewed in reference 40). Xrn1p is not an essential protein, probably reflecting its partial redundancy with factors required for a 3Ј degradation pathway (6, 21).On the other hand, Rat1p activity in the nucleus is essential. The enzyme acts in numerous RNA 5Ј processing reactions important for ribosome biogenesis. These include maturation of 5.8S rRNA (16) and 5Ј trimming of intron-encoded and polycistronic small nucleolar RNAs (snoRNAs) (30, 32). Interestingly, many of the known Rat1p-mediated reactions can be accomplished to some extent by Xrn1p, and thus, the observation of processing intermediates requires double mutants of XRN1 and RAT1 (30,32).RAT1 has been identified from a variety of genetic and biochemical ap...

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Human helicase geneSKI2Win the HLA class III region exhibits striking structural similarities to the yeast antiviral geneSKI2and to the human geneKIAA0052:emergence of a new gene family

Cited by 61 publications

References 48 publications

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

Linking the 3′ Poly(A) Tail to the Subunit Joining Step of Translation Initiation: Relations of Pab1p, Eukaryotic Translation Initiation Factor 5B (Fun12p), and Ski2p-Slh1p

Saccharomyces cerevisiae RAI1 (YGL246c) Is Homologous to Human DOM3Z and Encodes a Protein That Binds the Nuclear Exoribonuclease Rat1p

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