Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.13.1 (exoribonuclease)
 732 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The poly(A) tail shortening in mRNA, called deadenylation, is the first rate-limiting step in eukaryotic mRNA turnover, and the polyadenylate-binding protein (PABP) appears to be involved in the regulation of this step. However, the precise role of PABP remains largely unknown in higher eukaryotes. Here we identified and characterized a human PABP-dependent poly(A) nuclease (hPAN) complex consisting of catalytic hPan2 and regulatory hPan3 subunits. hPan2 has intrinsically a 3' to 5' exoribonuclease activity and requires Mg2+ for the enzyme activity. On the other hand, hPan3 interacts with PABP to simulate hPan2 nuclease activity. Interestingly, the hPAN nuclease complex has a higher substrate specificity to poly(A) RNA upon its association with PABP. Consistent with the roles of hPan2 and hPan3 in mRNA decay, the two subunits exhibit cytoplasmic co-localization. Thus, the human PAN complex is a poly(A)-specific exoribonuclease that is stimulated by PABP in the cytoplasm.
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PMID:Identification of a human cytoplasmic poly(A) nuclease complex stimulated by poly(A)-binding protein. 1458 2

The nuclear exosome functions in a variety of pathways catalyzing formation of mature RNA 3'-ends or the destruction of aberrant RNA transcripts. The RNA 3'-end formation activity of the exosome appeared restricted to small noncoding RNAs. However, the nuclear exosome controls the level of the mRNA encoding the poly(A)-binding protein Nab2p in a manner requiring an A(26) sequence in the mRNA 3' untranslated regions (UTR), and the activities of Nab2p and the exosome-associated exoribonuclease Rrp6p. Here we show that the A(26) sequence inhibits normal 3'-end processing of NAB2 mRNA in vivo and in vitro, and makes formation of the mature 3'-end dependent on trimming of the transcript by the core exosome and the Trf4p component of the TRAMP complex from a downstream site. The detection of mature, polyadenylated transcripts ending at, or within, the A(26) sequence indicates that exosome trimming sometimes gives way to polyadenylation of the mRNA. Alternatively, Rrp6p and the TRAMP-associated Mtr4p degrade these transcripts thereby limiting the amount of Nab2p in the cell. These findings suggest that NAB2 mRNA 3'-end formation requires the exosome and TRAMP complex, and that competition between polyadenylation and Rrp6p-dependent degradation controls the level of this mRNA.
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PMID:Regulation of NAB2 mRNA 3'-end formation requires the core exosome and the Trf4p component of the TRAMP complex. 1936 24