Yu Bin, Bi Liu, Zheng Binglian, Ji Lijuan, Chevalier David, Agarwal Manu, Ramachandran Vanitharani, Li Wanxiang, Lagrange Thierry, Walker John C, Chen Xuemei
Department of Botany and Plant Sciences, Institute of Integrative Genome Biology, University of California, Riverside, CA 92521, USA.
Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):10073-8. doi: 10.1073/pnas.0804218105. Epub 2008 Jul 15.
Proteins containing the forkhead-associated domain (FHA) are known to act in biological processes such as DNA damage repair, protein degradation, and signal transduction. Here we report that DAWDLE (DDL), an FHA domain-containing protein in Arabidopsis, acts in the biogenesis of miRNAs and endogenous siRNAs. Unlike mutants of genes known to participate in the processing of miRNA precursors, such as dcl1, hyponastic leaves1, and serrate, ddl mutants show reduced levels of pri-miRNAs as well as mature miRNAs. Promoter activity of MIR genes, however, is not affected by ddl mutations. DDL is an RNA binding protein and is able to interact with DCL1. In addition, we found that SNIP1, the human homolog of DDL, is involved in miRNA biogenesis and interacts with Drosha. Therefore, we uncovered an evolutionarily conserved factor in miRNA biogenesis. We propose that DDL participates in miRNA biogenesis by facilitating DCL1 to access or recognize pri-miRNAs.
已知含有叉头相关结构域（FHA）的蛋白质参与DNA损伤修复、蛋白质降解和信号转导等生物学过程。在此，我们报道拟南芥中一种含有FHA结构域的蛋白质DAWDLE（DDL）在miRNA和内源性siRNA的生物合成中发挥作用。与已知参与miRNA前体加工的基因突变体（如dcl1、下胚轴叶片1和锯齿状）不同，ddl突变体中初级miRNA（pri-miRNA）以及成熟miRNA的水平均降低。然而，MIR基因的启动子活性不受ddl突变的影响。DDL是一种RNA结合蛋白，能够与DCL1相互作用。此外，我们发现DDL在人类中的同源物SNIP1参与miRNA生物合成并与Drosha相互作用。因此，我们发现了miRNA生物合成中一个进化上保守的因子。我们提出DDL通过促进DCL1接近或识别pri-miRNA来参与miRNA生物合成。
