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Nuclear mRNA surveillance in THO/sub2 mutants is triggered by inefficient polyadenylation.
Mol Cell. 2008 Jul 11; 31(1):91-103.MC

Abstract

The yeast THO complex and the associated RNA helicase Sub2p are important mRNP maturation factors. Transcripts produced in THO/sub2 mutants are subject to degradation by a surveillance mechanism that involves the nuclear RNA exosome. Here we show that inefficient polyadenylation forms the basis of this accelerated mRNA decay. A genetic screen reveals extensive interactions between deletions of THO subunits and mRNA 3' end processing mutants. Nuclear run-ons strengthen this link by showing premature transcription termination close to polyadenylation sites in THO/sub2 mutants in vivo. Moreover, in vitro, pre-mRNA substrates are poorly polyadenylated and consequently unstable in extracts from THO/sub2 mutant strains. Decreased polyadenylation correlates with a specific downregulation of the poly(A)-polymerase cofactor Fip1p by the ubiquitin/proteasome pathway. Both polyadenylation defects and Fip1p instability depend on the nuclear exosome component Rrp6p and its activator Trf4p. We suggest that removal of aberrant mRNA is facilitated by direct regulation of polyadenylation activity.

Authors+Show Affiliations

Centre for mRNP Biogenesis and Metabolism, Aarhus University, C.F. Møllers Alle, Building 130, DK-8000 Aarhus C, Denmark.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18614048

Citation

Saguez, Cyril, et al. "Nuclear mRNA Surveillance in THO/sub2 Mutants Is Triggered By Inefficient Polyadenylation." Molecular Cell, vol. 31, no. 1, 2008, pp. 91-103.
Saguez C, Schmid M, Olesen JR, et al. Nuclear mRNA surveillance in THO/sub2 mutants is triggered by inefficient polyadenylation. Mol Cell. 2008;31(1):91-103.
Saguez, C., Schmid, M., Olesen, J. R., Ghazy, M. A., Qu, X., Poulsen, M. B., Nasser, T., Moore, C., & Jensen, T. H. (2008). Nuclear mRNA surveillance in THO/sub2 mutants is triggered by inefficient polyadenylation. Molecular Cell, 31(1), 91-103. https://doi.org/10.1016/j.molcel.2008.04.030
Saguez C, et al. Nuclear mRNA Surveillance in THO/sub2 Mutants Is Triggered By Inefficient Polyadenylation. Mol Cell. 2008 Jul 11;31(1):91-103. PubMed PMID: 18614048.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nuclear mRNA surveillance in THO/sub2 mutants is triggered by inefficient polyadenylation. AU - Saguez,Cyril, AU - Schmid,Manfred, AU - Olesen,Jens Raabjerg, AU - Ghazy,Mohamed Abd El-Hady, AU - Qu,Xiangping, AU - Poulsen,Mathias Bach, AU - Nasser,Tommy, AU - Moore,Claire, AU - Jensen,Torben Heick, PY - 2007/05/27/received PY - 2007/12/23/revised PY - 2008/04/29/accepted PY - 2008/7/11/pubmed PY - 2008/8/5/medline PY - 2008/7/11/entrez SP - 91 EP - 103 JF - Molecular cell JO - Mol Cell VL - 31 IS - 1 N2 - The yeast THO complex and the associated RNA helicase Sub2p are important mRNP maturation factors. Transcripts produced in THO/sub2 mutants are subject to degradation by a surveillance mechanism that involves the nuclear RNA exosome. Here we show that inefficient polyadenylation forms the basis of this accelerated mRNA decay. A genetic screen reveals extensive interactions between deletions of THO subunits and mRNA 3' end processing mutants. Nuclear run-ons strengthen this link by showing premature transcription termination close to polyadenylation sites in THO/sub2 mutants in vivo. Moreover, in vitro, pre-mRNA substrates are poorly polyadenylated and consequently unstable in extracts from THO/sub2 mutant strains. Decreased polyadenylation correlates with a specific downregulation of the poly(A)-polymerase cofactor Fip1p by the ubiquitin/proteasome pathway. Both polyadenylation defects and Fip1p instability depend on the nuclear exosome component Rrp6p and its activator Trf4p. We suggest that removal of aberrant mRNA is facilitated by direct regulation of polyadenylation activity. SN - 1097-4164 UR - https://www.unboundmedicine.com/medline/citation/18614048/Nuclear_mRNA_surveillance_in_THO/sub2_mutants_is_triggered_by_inefficient_polyadenylation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1097-2765(08)00418-8 DB - PRIME DP - Unbound Medicine ER -