Conserved motifs in both CPSF73 and CPSF100 are required to assemble the active endonuclease for histone mRNA 3′-end maturation
Conserved motifs in both CPSF73 and CPSF100 are required to assemble the active endonuclease for histone mRNA 3′-end maturation
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DOI：
10.1038/embor.2008.146
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发表时间：
2008-09-01
期刊：
影响因子：
7.7
通讯作者：
Steitz, Joan A.
中科院分区：
文献类型：
--
作者：
Kolev, Nikolay G.;Yario, Therese A.;Steitz, Joan A.
在真核生物中，信使RNA 3 '端形成的过程涉及转录物的核酸内切切割，然后合成聚腺苷酸尾。参与该成熟过程的复杂机制包含金属β-内酰胺酶（MBL）超家族的两种蛋白质，即裂解和多腺苷酸化特异性因子（CPSF）的73和100 kDa亚基。通过使用体外系统来评估这两种哺乳动物蛋白质中的点突变，我们发现来自两种多肽的MBL基序的保守残基是切割组蛋白前体mRNA的内切核酸酶活性的组装所需的。这表明CPSF 73和CPSF 100在真核前信使RNA的成熟过程中一起起作用，类似于MBL家族的其他成员，RNA酶Z和J，其作为同源二聚体起作用。
In eukaryotes, the process of messenger RNA 3'-end formation involves endonucleolytic cleavage of the transcript followed by synthesis of the poly(A) tail. The complex machinery involved in this maturation process contains two proteins of the metallo-beta-lactamase (MBL) superfamily, the 73 and 100 kDa subunits of the cleavage and polyadenylation specificity factor (CPSF). By using an in vitro system to assess point mutations in these two mammalian proteins, we found that conserved residues from the MBL motifs of both polypeptides are required for assembly of the endonuclease activity that cleaves histone pre-mRNAs. This indicates that CPSF73 and CPSF100 act together in the process of maturation of eukaryotic pre-messenger RNAs, similar to other members of the MBL family, RNases Z and J, which function as homodimers.