Bergman Naomi, Moraes Karen C M, Anderson John R, Zaric Bozidarka, Kambach Christian, Schneider Robert J, Wilusz Carol J, Wilusz Jeffrey
Department of Microbiology, Immunology & Pathology, Colorado State University, Fort Collins, Colorado 80525, USA.
Nat Struct Mol Biol. 2007 Sep;14(9):824-31. doi: 10.1038/nsmb1287. Epub 2007 Aug 12.
Many orthopoxvirus messenger RNAs have an unusual nontemplated poly(A) tract of 5 to 40 residues at the 5' end. The precise function of this feature is unknown. Here we show that 5' poly(A) tracts are able to repress RNA decay by inhibiting 3'-to-5' exonucleases as well as decapping of RNA substrates. UV cross-linking analysis demonstrated that the Lsm complex associates with the 5' poly(A) tract. Furthermore, recombinant Lsm1-7 complex specifically binds 5' poly(A) tracts 10 to 21 nucleotides in length, consistent with the length of 5' poly(A) required for stabilization. Knockdown of Lsm1 abrogates RNA stabilization by the 5' poly(A) tract. We propose that the Lsm complex simultaneously binds the 3' and 5' ends of these unusual messenger RNAs and thereby prevents 3'-to-5' decay. The implications of this phenomenon for cellular mRNA decay are discussed.
许多正痘病毒信使核糖核酸（mRNA）在5'端有一段长度为5至40个残基的不寻常的非模板化聚腺苷酸（poly(A)）序列。这一特征的确切功能尚不清楚。在此，我们表明5'端的poly(A)序列能够通过抑制3'至5'核酸外切酶以及RNA底物的脱帽来抑制RNA降解。紫外线交联分析表明，Lsm复合物与5'端的poly(A)序列结合。此外，重组的Lsm1-7复合物特异性结合长度为10至21个核苷酸的5'端poly(A)序列，这与稳定所需的5'端poly(A)序列长度一致。敲低Lsm1可消除5'端poly(A)序列对RNA的稳定作用。我们提出，Lsm复合物同时结合这些不寻常信使RNA的3'端和5'端，从而防止3'至5'端降解。本文讨论了这一现象对细胞mRNA降解的影响。
