A 3' exonuclease that specifically interacts with the 3' end of histone mRNA.
Metazoan histone mRNAs end in a highly conserved stem-loop structure followed by ACCCA. Previous studies have suggested that the stem-loop binding protein (SLBP) is the only protein binding this region. Using RNA affinity purification, we identified a second protein, designated 3'hExo, that contains a SAP and a 3' exonuclease domain and binds the same sequence. Strikingly, 3'hExo can bind the stem-loop region both separately and simultaneously with SLBP. Binding of 3'hExo requires the terminal ACCCA, whereas binding of SLBP requires the 5' side of the stem-loop region. Recombinant 3'hExo degrades RNA substrates in a 3'-5' direction and has the highest activity toward the wild-type histone mRNA. Binding of SLBP to the stem-loop at the 3' end of RNA prevents its degradation by 3'hExo. These features make 3'hExo a primary candidate for the exonuclease that initiates rapid decay of histone mRNA upon completion and/or inhibition of DNA replication.
Dominski
Zbigniew
Z
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA. dominski@med.unc.edu
Yang
Xiao-cui
XC
Kaygun
Handan
H
Dadlez
Michal
M
Marzluff
William F
WF
D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D005092:Exonucleases / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry; D011817:Rabbits; D013997:Time Factors; D020798:Two-Hybrid System Techniques; D039221:mRNA Cleavage and Polyadenylation Factors
D006657:Histones; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C092663:SLBP protein, human; D039221:mRNA Cleavage and Polyadenylation Factors; D012313:RNA; D004247:DNA; D005092:Exonucleases; C022650:spleen exonuclease