Poly(A) Tail Shortening by a Mammalian Poly(A)-specific 3′-Exoribonuclease

Deciphering the cellular pathway for transport of poly(A)-binding protein II

“…Comparison of mammalian and yeast pre-mRNA 39-end-processing components reveals that, although many homologies can be found, the proteins are not function-ally interchangeable (for a recent review, see )+ An apparent case of divergence during evolution occurs with poly(A)-binding proteins+ Yeast contains a single poly(A)-binding protein (termed Pab1p), which is an essential protein present in both the nucleus and the cytoplasm (Sachs et al+, 1986)+ In the nucleus it stimulates polyadenylation and controls poly(A) tail length (Amrani et al+, 1997;MinvielleSebastia et al+, 1997;Brown & Sachs, 1998), whereas in the cytoplasm it is involved in translation initiation (Sachs & Davis, 1989;Sachs & Deardorff, 1992;Tarun & Sachs, 1995, 1996Le et al+, 1997) and mRNA degradation (Caponigro & Parker, 1995;Boeck et al+, 1998;Coller et al+, 1998)+ In contrast, mammalian cells contain two distinct proteins called poly(A)-binding protein I (PABP1) and poly(A)-binding protein II (PAB II or PABP2)+ PABP1 is predominantly detected in the cytoplasm (Görlach et al+, 1994), whereas PABP2 is localized in the nucleus (Wahle, 1991;Krause et al+, 1994)+ PABP1, which is the mammalian counterpart of yeast Pab1p (51% identity), is apparently involved in both cytoplasmic mRNA stability (Bernstein et al+, 1989;Wormington et al+, 1996;Afonina et al+, 1997;Ford et al+, 1997;Körner & Wahle, 1997) and translation (Craig et al+, 1998), but to date there is no evidence that it participates in nuclear pre-mRNA 39-end processing (see )+ Consistent with its nuclear localization, PABP2 is the mammalian protein involved in polyadenylation+ PABP2 stimulates processive poly(A) addition and controls the size of the tail to be ;250 nt in length (Wahle, 1991(Wahle, , 1995Bienroth et al+, 1993)+ How PABP2 bound to poly(A) tails in the nucleus is replaced by PABP1 in the cytoplasm remains unknown, but recent evidence indicates that both PABP1 and PABP2 shuttle between nucleus and cytoplasm (Afonina et al+, 1998;Chen et al+, 1999)+ Because it is not known when PABP1 exchanges with PABP2, one possibility is that PABP2 crosses the nuclear pores in association with the mRNA and dissoci...…”

p38 Mitogen-activated Protein Kinase Stabilizes mRNAs That Contain Cyclooxygenase-2 and Tumor Necrosis Factor AU-rich Elements by Inhibiting Deadenylation

“…A poly(A)-specific ribonuclease has been purified from calf thymus (8) and has very similar enzymatic properties to the activity in HeLa cells (9). In yeast there are two deadenylase complexes, Pan2p/Pan3p (41,42) and Ccr4p/Pop2p/Notp (43).…”

“…The default mRNA decay pathway in eukaryotes begins by shortening of the poly(A) tail (4 -7). A mammalian poly(A)-specific ribonuclease has been identified (8,9), and a human homologue of the major cytoplasmic deadenylase in yeast, Ccr4p, has been cloned (10). In mammalian cell extracts deadenylation is followed by decay of the mRNA body, which occurs mainly in the 3Ј 3 5Ј direction due to the action of a large exonuclease complex or exosome (11)(12)(13); the 5Ј cap structure of the mRNA then being removed by a scavenger activity (11).…”

A polysomal ribonuclease involved in the destabilization of albumin mRNA is a novel member of the peroxidase gene family

“…The term "messenger RNase" was coined by Ross & Kobs (1986) to describe ribonucleases whose primary function is to degrade mRNA+ In yeast, at least three enzymes or enzymatic activities are involved in mRNA turnover; a deadenylating nuclease, a decapping pyrophosphatase, and a 59-39 exonuclease+ Deadenylation precedes decapping, which is followed by degradation of the body of the mRNA by the 59-39 exonuclease Xrn1p (reviewed in Tharun & Parker, 1997)+ Although endonucleases might also be involved in yeast mRNA decay (Vreken & Raue, 1992), the predominant pathway appears to be exonucleolytic+ There is a growing body of evidence that some vertebrate mRNAs are degraded by a pathway similar to that described for yeast+ Many unstable vertebrate mRNAs undergo deadenylation followed by degradation of the mRNA body (reviewed in Ross, 1995;Schoenberg & Chernokalskaya, 1997)+ Moreover, several poly(A)-degrading exonucleases have been described (Åström et al+, 1991;Åström et al+ 1992;Caruccio & Ross, 1994;Koerner & Wahle, 1997), although their role, if any, in mRNA decay has not been proved+ Although a vertebrate decapping pyrophosphatase has yet to be found, the identification of mammalian Xrn1p (Bashkirov et al+, 1997) and evidence for decapping (Couttet et al+, 1997) indicate that the pathway of deadenylation r decapping r 59-39 decay is likely conserved in all eukaryotes+…”