多聚 A 聚合酶 Star-PAP 通过促进 CPSF 相互作用和对前体 mRNA 的特异性来控制 3'-末端切割。
The poly A polymerase Star-PAP controls 3'-end cleavage by promoting CPSF interaction and specificity toward the pre-mRNA.
机构信息
Department of Pharmacology, University of Wisconsin, Medical Science Center, Madison, WI 53706, USA.
出版信息
EMBO J. 2010 Dec 15;29(24):4132-45. doi: 10.1038/emboj.2010.287. Epub 2010 Nov 19.
Abstract
Star-PAP is a poly (A) polymerase (PAP) that is putatively required for 3'-end cleavage and polyadenylation of a select set of pre-messenger RNAs (mRNAs), including heme oxygenase (HO-1) mRNA. To investigate the underlying mechanism, the cleavage and polyadenylation of pre-mRNA was reconstituted with nuclear lysates. siRNA knockdown of Star-PAP abolished cleavage of HO-1, and this phenotype could be rescued by recombinant Star-PAP but not PAPα. Star-PAP directly associated with cleavage and polyadenylation specificity factor (CPSF) 160 and 73 subunits and also the targeted pre-mRNA. In vitro and in vivo Star-PAP was required for the stable association of CPSF complex to pre-mRNA and then CPSF 73 specifically cleaved the mRNA at the 3'-cleavage site. This mechanism is distinct from canonical PAPα, which is recruited to the cleavage complex by interacting with CPSF 160. The data support a model where Star-PAP binds to the RNA, recruits the CPSF complex to the 3'-end of pre-mRNA and then defines cleavage by CPSF 73 and subsequent polyadenylation of its target mRNAs.
摘要
Star-PAP 是一种多聚（A）聚合酶（PAP），它被假定为一组特定的前信使 RNA（mRNA），包括血红素加氧酶（HO-1）mRNA 的 3'-末端切割和多聚腺苷酸化所必需的。为了研究潜在的机制，使用核裂解物重新进行了前体 mRNA 的切割和多聚腺苷酸化。Star-PAP 的 siRNA 敲低消除了 HO-1 的切割，并且这种表型可以被重组 Star-PAP 挽救，但不能被 PAPα 挽救。Star-PAP 直接与切割和多聚腺苷酸化特异性因子（CPSF）160 和 73 亚基以及靶向的前体 mRNA 结合。在体外和体内，Star-PAP 都需要 CPSF 复合物稳定地结合到前体 mRNA 上，然后 CPSF 73 特异性地在 3'-切割位点切割 mRNA。这种机制与经典的 PAPα 不同，后者通过与 CPSF 160 相互作用被招募到切割复合物中。数据支持这样一种模型，即 Star-PAP 结合到 RNA 上，招募 CPSF 复合物到前体 mRNA 的 3'-末端，然后由 CPSF 73 定义切割，并随后对其靶 mRNAs 进行多聚腺苷酸化。
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