Cytoplasmic poly(A) binding protein-1 binds to genomically encoded sequences within mammalian mRNAs.
Cytoplasmic poly(A) binding protein-1 binds to genomically encoded sequences within mammalian mRNAs.
复制标题
DOI：
10.1261/rna.053447.115
复制
发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Liebhaber SA
中科院分区：
文献类型：
--
作者：
Kini HK;Silverman IM;Ji X;Gregory BD;Liebhaber SA
主要哺乳动物细胞质 Poly(A) 结合蛋白 PABPC1 的功能主要通过其与 mRNA 3' Poly(A) 尾的结合来表征。这些相互作用通过增强翻译和 mRNA 稳定性，在转录后基因调控中发挥重要作用。在这里，我们进行了全转录组 CLIP-seq 分析，以确定基因组编码的 mRNA 序列中可能影响基因调控的其他 PABPC1 结合位点。通过该分析，我们发现 PABPC1 直接与小鼠转录组中数千个 mRNA 中的典型聚腺苷酸化信号结合。 PABPC1 结合还映射到包含开放阅读框的翻译起始和终止位点，在复制依赖性组蛋白 mRNA 中体现得最明显。此外，PABPC1 相互作用位点的一个更受限制的子集包含 mRNA 5'UTR 内富含 A 的序列，包括 Pabpc1 mRNA 本身。功能分析表明，5' UTR 中的这些 PABPC1 相互作用介导自动调节和反式调节翻译控制。总的来说，这些发现揭示了 PABPC1 结合的全部内容，其范围比以前认识的要广泛得多，并且具有影响和协调对广泛细胞功能至关重要的转录后控制的相应潜力。
The functions of the major mammalian cytoplasmic poly(A) binding protein, PABPC1, have been characterized predominantly in the context of its binding to the 3′ poly(A) tails of mRNAs. These interactions play important roles in post-transcriptional gene regulation by enhancing translation and mRNA stability. Here, we performed transcriptome-wide CLIP-seq analysis to identify additional PABPC1 binding sites within genomically encoded mRNA sequences that may impact on gene regulation. From this analysis, we found that PABPC1 binds directly to the canonical polyadenylation signal in thousands of mRNAs in the mouse transcriptome. PABPC1 binding also maps to translation initiation and termination sites bracketing open reading frames, exemplified most dramatically in replication-dependent histone mRNAs. Additionally, a more restricted subset of PABPC1 interaction sites comprised A-rich sequences within the 5′ UTRs of mRNAs, including Pabpc1 mRNA itself. Functional analyses revealed that these PABPC1 interactions in the 5′ UTR mediate both auto- and trans-regulatory translational control. In total, these findings reveal a repertoire of PABPC1 binding that is substantially broader than previously recognized with a corresponding potential to impact and coordinate post-transcriptional controls critical to a broad array of cellular functions.