U1A inhibits cleavage at the immunoglobulin m heavy-chain secretory poly(A) site by binding between the two downstream GU-rich regions

U1A inhibits cleavage at the immunoglobulin m heavy-chain secretory poly(A) site by binding between the two downstream GU-rich regions
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DOI:
10.1128/mcb.24.14.6162-6171.2004
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发表时间:
2004-07-01
影响因子:
5.3
通讯作者:
Gunderson, SI
Gunderson, SI
中科院分区:
生物学2区
文献类型:
--
作者:
Phillips, C;Pachikara, N;Gunderson, SI

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免疫球蛋白M重链基因座含有两个poly(A)位点,其在B细胞分化期间交替表达。尽管其启动子近端的位置,分泌聚(A)的网站是不表达在未分化的细胞。在B细胞分化过程中,对分泌性poly(A)位点的激活至关重要的是裂解刺激因子64 K与poly(A)位点下游富含GU的元件结合的变化。是什么调节了这种变化还不清楚。分泌性多聚腺苷酸位点含有两个下游富含谷氨酰胺的区域,由29个核苷酸的序列隔开。这两个富含GU的区域对于特异性切割-聚腺苷酸化复合物的结合是必需的。我们在这里证明,U1 A结合两个(AUGCN(1-3)C)基序内的29个核苷酸的序列,并抑制切割刺激因子64 K的结合和切割的分泌聚(A)的网站。
The immunoglobulin M heavy-chain locus contains two poly(A) sites which are alternatively expressed during B-cell differentiation. Despite its promoter proximal location, the secretory poly(A) site is not expressed in undifferentiated cells. Crucial to the activation of the secretory poly(A) site during B-cell differentiation are changes in the binding of cleavage stimulatory factor 64K to GU-rich elements downstream of the poly(A) site. What regulates this change is not understood. The secretory poly(A) site contains two downstream GU-rich regions separated by a 29-nucleotide sequence. Both GU-rich regions are necessary for binding of the specific cleavage-polyadenylation complex. We demonstrate here that U1A binds two (AUGCN(1-3)C) motifs within the 29-nucleotide sequence and inhibits the binding of cleavage stimulatory factor 64K and cleavage at the secretory poly(A) site.