Dong Shuyun, Li Chunfang, Zenklusen Daniel, Singer Robert H, Jacobson Allan, He Feng
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Mol Cell. 2007 Feb 23;25(4):559-73. doi: 10.1016/j.molcel.2007.01.012.
Autoregulatory loops often provide precise control of the level of expression of specific genes that encode key regulatory proteins. Here we have defined a pathway by which Yra1p, a yeast mRNA export factor, controls its own expression. We show that YRA1 exon 1 sequences in cis and Yra1p in trans inhibit YRA1 pre-mRNA splicing and commit the pre-mRNA to nuclear export. Mex67p and Crm1p jointly promote YRA1 pre-mRNA export, and once in the cytoplasm, the pre-mRNA is degraded by a 5' to 3' decay mechanism that is dependent on the decapping activator Edc3p and on specific sequences in the YRA1 intron. These results illustrate how common steps in the nuclear processing, export, and degradation of a transcript can be uniquely combined to control the expression of a specific gene and suggest that Edc3p-mediated decay may have additional regulatory functions in eukaryotic cells.
自调控回路通常能精确控制编码关键调控蛋白的特定基因的表达水平。在此，我们确定了一条酵母mRNA输出因子Yra1p控制自身表达的途径。我们发现，顺式的YRA1外显子1序列和反式的Yra1p抑制YRA1前体mRNA的剪接，并使前体mRNA进入核输出过程。Mex67p和Crm1p共同促进YRA1前体mRNA的输出，并且一旦进入细胞质，前体mRNA就会通过依赖于脱帽激活因子Edc3p和YRA1内含子中特定序列的5'到3'衰变机制被降解。这些结果说明了转录本在核加工、输出和降解过程中的常见步骤是如何独特地组合起来以控制特定基因的表达，并表明Edc3p介导的衰变可能在真核细胞中具有额外的调控功能。
