Antisense transcription regulates the expression of sense gene via alternative polyadenylation.
Antisense transcription regulates the expression of sense gene via alternative polyadenylation.
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反义转录通过选择性多腺苷酸化调节有义基因的表达。
DOI：
10.1007/s13238-017-0497-0
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发表时间：
2018-06
期刊：
影响因子：
21.1
通讯作者：
Ni T
中科院分区：
文献类型：
--
作者：
Shen T;Li H;Song Y;Yao J;Han M;Yu M;Wei G;Ni T
信使RNA的天然反义转录本(NAT)和选择性多聚腺苷酸化(APA)是转录组复杂性的重要贡献者，每一个都在多种生物学过程中发挥着关键作用。然而，它们是否具有串扰和协同作用尚不清楚。我们发现APA富含人类正义-反义(S-AS)基因对，并最终聚焦于RNASE_2C-KAT5 S-AS对进行进一步研究。在顺式而非反式中，反义KAT5基因的过表达促进了正义基因RNASEH_2C的远端Polya(PA)位点的利用，从而产生了更长的3‘非翻译区(3’UTR)，并产生了更少的蛋白质，并伴随着细胞生长的减慢。从机制上讲，Pol II占位率的升高和SRSF3的结合可以解释Pa远端部位使用率较高的原因。最后，NAT对RNASE_2C-KAT5中正义基因蛋白水平的下调是人所特有的，而不是小鼠所特有的，因为人而不是小鼠缺少RNASE_2C远端的PA位点。我们首次提供了证据，支持某些基因可能不是通过自身的蛋白质影响表型，而是通过APA影响其重叠基因的表达，这意味着对理解基因与表型之间的联系有一种意想不到的观点。本文的在线版本(10.1007/s13238-0170497-0)包含补充材料，可供授权用户使用。
Natural antisense transcripts (NAT) and alternative polyadenylation (APA) of messenger RNA (mRNA) are important contributors of transcriptome complexity, each playing a critical role in multiple biological processes. However, whether they have crosstalk and function collaboratively is unclear. We discovered that APA enriched in human sense-antisense (S-AS) gene pairs, and finally focused on RNASEH2C-KAT5 S-AS pair for further study. In cis but not in trans over-expression of the antisense KAT5 gene promoted the usage of distal polyA (pA) site in sense gene RNASEH2C, which generated longer 3′ untranslated region (3′UTR) and produced less protein, accompanying with slowed cell growth. Mechanistically, elevated Pol II occupancy coupled with SRSF3 could explain the higher usage of distal pA site. Finally, NAT-mediated downregulation of sense gene’s protein level in RNASEH2C-KAT5 pair was specific for human rather than mouse, which lacks the distal pA site of RNASEH2C. We provided the first evidence to support that certain gene affected phenotype may not by the protein of its own, but by affecting the expression of its overlapped gene through APA, implying an unexpected view for understanding the link between genotype and phenotype. The online version of this article (10.1007/s13238-017-0497-0) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
Carrieri, Claudia;Cimatti, Laura;Gustincich, Stefano
通讯作者：
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影响因子：
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影响因子：
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作者：
Gunderson, SI;Polycarpou-Schwarz, M;Mattaj, IW
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影响因子：
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作者：
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通讯作者：
Mayr C
DOI：
10.1073/pnas.0808480105
发表时间：
2008-10-14
影响因子：
11.1
作者：
Jao, Cindy Y.;Salic, Adrian
通讯作者：
Salic, Adrian