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Regulation of Degradation of Histone mRNA
Author(s) -
Marzluff William F.,
Mullen Thomas E.,
Kaygun Handan
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.527.1
Subject(s) - nonsense mediated decay , histone , histone h2a , microbiology and biotechnology , histone methyltransferase , biology , messenger rna , polyadenylation , chemistry , rna , dna , genetics , rna splicing , gene
The replication‐dependent histone mRNAs are the only eukaryotic mRNAs that are not polyadenylated, ending instead in a conserved stem‐loop. Histone mRNAs are present in high levels only in S‐phase, and they are regulated coordinately with DNA replication. A major regulatory step is the rapid degradation of histone mRNA when DNA replication is inhibited or at the end of S‐phase. We have elucidated the pathway of histone mRNA degradation. ATR, a kinase activated when DNA synthesis is inhibited, is required for histone mRNA degradation, although the intermediate steps in signaling that ultimately initiate histone mRNA degradation are not known. The stemloop must be close (25–75 nts) to the termination codon for efficient regulation of translation and the mRNA must be actively translated. The protein that binds the stem‐loop, SLBP, is involved in translation and is likely a target of the signaling pathway that activates histone mRNA degradation, as a result of inefficient translation termination. The inefficient termination leads to the recruitment of Upf1, the critical factor also required for nonsense mediated decay. A terminal uridyl transferase (TUTase) is then recruited and 8–12 U's added to the end of the histone mRNA. This provides a platform for binding Lsm1‐7, which in turn recruit the decapping enzymes, as well as the exosome to degrade individual histone molecules simultaneously from both ends.