Tissue-specific autoregulation of Drosophila suppressor of forked by alternative poly(A) site utilization leads to accumulation of the suppressor of forked protein in mitotically active cells
Tissue-specific autoregulation of Drosophila suppressor of forked by alternative poly(A) site utilization leads to accumulation of the suppressor of forked protein in mitotically active cells
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DOI：
10.1017/s1355838200001266
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发表时间：
2000-11-01
期刊：
影响因子：
4.5
通讯作者：
Simonelig, M
中科院分区：
文献类型：
--
作者：
Juge, F;Audibert, A;Simonelig, M
分叉蛋白的抑制因子是人类切割刺激因子77K亚基的果蝇同源物，这是mRNA 3'端加工反应的第一步所需的复合物。我们之前已经证明，野生型su(f)功能需要在该基因的内含子4中积累被聚腺苷化的截断的su(f)转录物。这使我们提出了一个模型，其中Su(f)蛋白会通过刺激这种截断的Su(f) RNA的3'端形成来负性调节其自身的积累。在本文中，我们证明了这个模型，并表明Su(f)的自动调节是组织特异性的。我们发现，Su(f)蛋白的这种分布是由于Su(f)刺激了Su(f)内含子多聚(a)位点的组织特异性利用，导致截断的Su(f)转录物在非分裂组织中积累，该内含子多聚(a)位点的利用在Su(f)突变体中受到影响，并在转基因编码野生型Su(f)蛋白的突变体中恢复。这些数据提供了通过poly(a)位点选择对蛋白质水平的细胞类型特异性调节的体内例子，并证实了Su(f)在poly(a)位点利用调节中的作用。
The Suppressor of forked protein is the Drosophila homolog of the 77K subunit of human cleavage stimulation factor, a complex required for the first step of the mRNA 3'-end-processing reaction, We have shown previously that wild-type su(f) function is required for the accumulation of a truncated su(f) transcript polyadenylated in intron 4 of the gene. This led us to propose a model in which the Su(f) protein would negatively regulate its own accumulation by stimulating 3'-end formation of this truncated su(f) RNA, In this article, we demonstrate this model and show that su(f) autoregulation is tissue specific. The Su(f) protein accumulates at a high level in dividing tissues, but not in nondividing tissues, We show that this distribution of the Su(f) protein results from stimulation by Su(f) of the tissue-specific utilization of the su(f) intronic poly(A) site, leading to the accumulation of the truncated su(f) transcript in nondividing tissues, Utilization of this intronic poly(A) site is affected in a su(f) mutant and restored in the mutant with a transgene encoding wild-type Su(f) protein, These data provide an in vivo example of cell-type-specific regulation of a protein level by poly(A) site choice, and confirm the role of Su(f) in regulation of poly(A) site utilization.