Cap-dependent deadenylation of mRNA

Abstract

is also initiated by deadenylation (Wilson and Treisman, D-35392 Giessen, Germany and 3 Department of Biology, University of 1988; Shyu et al., 1991; Chen and Shyu, 1995 1996). During oocyte maturation, deadenylation does not are not detectable in the enzyme preparation, and require specific cis-elements and is a default pathway PARN itself binds to m 7 GTP-Sepharose and is eluted for mRNAs that do not undergo compensatory poly(A) specifically with the cap analog m 7 GTP. Xenopus PARN elongation (Fox and Wickens, 1990; Varnum and is known to catalyze mRNA deadenylation during Wormington, 1990). In contrast, certain mRNAs which oocyte maturation. The enzyme is depleted from oocyte are polyadenylated during meiotic maturation contain extract with m 7 GTP-Sepharose, can be photocross-3Ј-UTR elements that promote their subsequent deadenyllinked to the m 7 GpppG cap and deadenylates ation after fertilization. Thus, the translation of these m 7 GpppG-capped RNAs more efficiently than ApppGmRNAs is restricted to mature oocytes (Bouvet et al., capped RNAs both in vitro and in vivo. These data 1994; Legagneux et al., 1995). In both cases, deadenylation provide additional evidence that PARN is responsible does not destabilize mRNAs immediately, but is a prefor deadenylation during oocyte maturation and sugrequisite for their degradation at later stages of developgest that interactions between 5Ј cap and 3Ј poly(A) ment (Audic et al., 1997; Gillian-Daniel et al., 1998; tail may integrate translational efficiency with mRNA Voeltz and Steitz, 1998). The uncoupling of deadenylation stability.from mRNA decay in gametes and embryos contrasts with Keywords: cap structure/deadenylation/mRNA stability/ both yeast and metazoan cells in which poly(A) removal oocyte maturation/poly(A) tails rapidly promotes mRNA degradation. Both the dependence of decapping on prior deadenylation and the inhibition of translation initiation by poly(A)

Identification of the Active Site of Poly(A)-specific Ribonuclease by Site-directed Mutagenesis and Fe2+-mediated Cleavage

“…The cap interacting and poly(A) degrading properties of PARN also provide evidence that PARN may play a role in controlling initiation of protein synthesis (3, 6 -8). Besides a possible role in controlling translation, the mRNA cap binding property of PARN has a direct role in stimulating PARN degradation efficiency (3,6,7) and in amplifying the processive mode of degradation (8). We have recently proposed a simple model for how PARN operates (8).…”

Coordination of Divalent Metal Ions in the Active Site of Poly(A)-specific Ribonuclease

“…homotrimer) (6), and interacts with both the 3Ј-end-located poly(A) tail and the 5Ј-end cap structure during degradation (6 -9). The interaction with the 5Ј-end cap structure enhances the rate of degradation (6,7,9) and amplifies the processivity of PARN activity (9). The functional significance of PARN is still unknown, although its high specificity for poly(A) and interaction with the cap structure provide strong arguments for PARN being involved in mammalian mRNA poly(A) tail degradation and therefore could play important roles in mRNA decay and initiation of protein synthesis (6 -9).…”

CUG-BP and 3'UTR sequences influence PARN-mediated deadenylation in mammalian cell extracts

“…Numerous candidate deadenylases have been identified to date in mammalian cells. PARN (Poly(A)-specific 3'-to-5' exoRiboNuclease), whose activity is readily demonstrable in extracts (Korner and Wahle, 1997;Korner et al 1998), exhibits an interesting interaction with the 5' cap of transcripts that influences its processivity (Dehlin et al, 2000;Gao et al, 2000;Martinez et al, 2001). In addition, PARN co-purifies with several components of the mRNA decay machinery (Lejeune et al, 2003).…”