在1月1日的Genes & Development雜志上,,Thomas Mullen和William Marzluff博士通過研究揭示出了哺乳動(dòng)物組蛋白mRNA的降解原理。
組蛋白mRNA在S期末會(huì)迅速降解,,但是這個(gè)過程的生物學(xué)機(jī)制一直含糊不清,因?yàn)楹笊鷦?dòng)物的組蛋白mRNAs有一個(gè)非常獨(dú)特的結(jié)構(gòu):不是典型的3' poly(A)尾,,而是一段保守的3'莖環(huán)結(jié)構(gòu),。
Mullen和Marzluff博士的研究成果表明,當(dāng)一些尿苷添加到組蛋白mRNAs的3'端后,,轉(zhuǎn)錄產(chǎn)物就會(huì)去帽(decapped),,并從兩端開始降解。參與降解的是普通的mRNA衰變機(jī)器(mRNA decay machinery),。
此項(xiàng)工作也是首次展示了寡聚尿苷化對(duì)哺乳動(dòng)物mRNA轉(zhuǎn)錄產(chǎn)物半衰期的調(diào)控,。
資料來源:Cold Spring Harbor Laboratory
生物谷推薦原始出處:
GENES & DEVELOPMENT 22:50-65, 2008
Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to 5'
Thomas E. Mullen1 and William F. Marzluff1,2,3
1 Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; 2 Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Histone mRNAs are rapidly degraded at the end of S phase or when DNA replication is inhibited. Histone mRNAs end in a conserved stem–loop rather than a poly(A) tail. Degradation of histone mRNAs requires the stem–loop sequence, which binds the stem–loop-binding protein (SLBP), active translation of the histone mRNA, and the location of the stem–loop close to the termination codon. We report that the initial step in histone mRNA degradation is the addition of uridines to the 3' end of the histone mRNA, both after inhibition of DNA replication and at the end of S phase. Lsm1 is required for histone mRNA degradation and is present in a complex containing SLBP on the 3' end of histone mRNA after inhibition of DNA replication. We cloned degradation intermediates that had been partially degraded from both the 5' and the 3' ends. RNAi experiments demonstrate that both the exosome and 5'-to-3' decay pathway components are required for degradation, and individual histone mRNAs are then degraded simultaneously 5' to 3' and 3' to 5'.
[Keywords: Histone; cell cycle; mRNA stability; decapping; exosome; oligouridylation]]
Received October 3, 2007; revised version accepted November 5, 2007.
3 Corresponding author.
E-MAIL [email protected] ; FAX (919) 962-1274.