title: ARE-mRNA degradation requires the 5'-3' decay pathway.
abstract: As an important mode of suppressing gene expression, messenger RNAs containing an AU-rich element (ARE) in the 3' untranslated region are rapidly degraded in the cytoplasm. ARE-mediated mRNA decay (AMD) is initiated by deadenylation, and in vitro studies have indicated that subsequent degradation occurs in the 3'-5' direction through a complex of exonucleases termed the exosome. An alternative pathway of mRNA degradation occurs at processing bodies, cytoplasmic foci that contain decapping enzymes, the 5'-3' exonuclease Xrn1 and the Lsm1-7 heptamer. To determine which of the two pathways is important for AMD in live cells, we targeted components of both pathways using short interfering RNA in human HT1080 cells. We show that Xrn1 and Lsm1 are essential for AMD. On the other side, out of three exosome components tested, only knockdown of PmScl-75 caused a strong inhibition of AMD. Our results show that mammalian cells, similar to yeast, require the 5'-3' Xrn1 pathway to degrade ARE-mRNAs.
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Smith 608, Boston, Massachusetts 02115, USA. gstoecklin@rics.bwh.harvard.edu
authors.forename: Georg
authors.initials: G
authors.lastname: Stoecklin
authors.forename: Thomas
authors.initials: T
authors.lastname: Mayo
authors.forename: Paul
authors.initials: P
authors.lastname: Anderson
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012315:RNA Caps; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements
chemical_list: D020413:3' Untranslated Regions; C464824:LSM1 protein, human; D011518:Proto-Oncogene Proteins; D012315:RNA Caps; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins