Human La protein: a stabilizer of histone mRNA.
Histone mRNA is destabilized at the end of S phase and in cell-free mRNA decay reaction mixtures supplemented with histone proteins, indicating that histones might autoregulate the histone mRNA half-life. Histone mRNA destabilization in vitro requires three components: polysomes, histones, and postpolysomal supernatant (S130). Polysomes are the source of the mRNA and mRNA-degrading enzymes. To investigate the role of the S130 in autoregulation, crude S130 was fractionated by histone-agarose affinity chromatography. Two separate activities affecting the histone mRNA half-life were detected. The histone-agarose-bound fraction contained a histone mRNA destabilizer that was activated by histone proteins; the unbound fraction contained a histone mRNA stabilizer. Further chromatographic fractionation of unbound material revealed only a single protein stabilizer, which was purified to homogeneity, partially sequenced, and found to be La, a well-characterized RNA-binding protein. When purified La was added to reaction mixtures containing polysomes, a histone mRNA decay intermediate was stabilized. This intermediate corresponded to histone mRNA lacking 12 nucleotides from its 3' end and containing an intact coding region. Anti-La antibody blocked the stabilization effect. La had little or no effect on several other cell cycle-regulated mRNAs. We suggest that La prolongs the histone mRNA half-life during S phase and thereby increases histone protein production.
McLaren
R S
RS
McArdle Laboratory for Cancer Research University of Wisconsin, Madison 53706, USA.
Caruccio
N
N
Ross
J
J
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D001324:Autoantigens / Q000302:isolation & purification / Q000378:metabolism*; D002846:Chromatography, Affinity; D006207:Half-Life; D006657:Histones / Q000235:genetics*; D006706:Homeostasis; D006801:Humans; D008954:Models, Biological; D011132:Polyribosomes / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000302:isolation & purification / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D000097585:SS-B Antigen
D000251:Adenosine Triphosphatases; D001324:Autoantigens; D006657:Histones; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D014157:Transcription Factors; D000097585:SS-B Antigen