Alternative splicing regulated by butyrate in bovine epithelial cells.
Alternative splicing regulated by butyrate in bovine epithelial cells.
复制标题
DOI：
10.1371/journal.pone.0039182
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Li RW
中科院分区：
文献类型：
--
作者：
Wu S;Li C;Huang W;Li W;Li RW
丁酸作为组蛋白脱乙酰酶(HDAC)的信号分子和抑制剂，除了在反刍动物能量代谢中发挥重要作用外，还对多种生物学过程产生影响，如细胞凋亡和细胞增殖。本研究利用RNA-SEQ技术研究了丁酸对牛上皮细胞选择性剪接的影响。在丁酸处理(BT)组和对照(CT)组之间，连接阅读分别占总映射阅读的11.28%和12.32%。≥3连接阅读支持检测到的201,326个潜在剪接连接。其中约94%与GT/AG一致，∼3%为GC/AG。未观察到AT/AC连接。总共检测到2,834个外显子跳过事件，至少有3个连接阅读支持。至少有7个基因的mRNA表达受丁酸的显著影响，它们的外显子跳跃事件也受到丁酸的差异调控。此外，在基因水平上被丁酸盐(Fdr<；0.001)诱导310倍的COL5A3，在Bt基因中定位于外显子8(供体)和外显子#11(受体)的连接读数显著增加。这一事件有可能导致COL5A3mRNA亚型的形成，69个外显子中有2个缺失。此外，还检测到了216个受丁酸调控的差异表达的转录异构体。例如，ORC1的亚型1被丁酸强烈抑制，而亚型2保持不变。丁酸盐在物理上结合并抑制除HDAC6和HDAC10以外的所有依赖锌的HDACs。我们的结果提供了证据，证明丁酸也通过其转录调控来调节经典的HDAC的脱乙酰酶活性。此外，还鉴定了13个受丁酸盐不同影响的基因融合事件。我们的结果提供了一个关于丁酸调节的复杂转录组动力学的快照，这将有助于我们理解丁酸盐和其他HDAC抑制剂的生物学效应。
As a signaling molecule and an inhibitor of histone deacetylases (HDACs), butyrate exerts its impact on a broad range of biological processes, such as apoptosis and cell proliferation, in addition to its critical role in energy metabolism in ruminants. This study examined the effect of butyrate on alternative splicing in bovine epithelial cells using RNA-seq technology. Junction reads account for 11.28 and 12.32% of total mapped reads between the butyrate-treated (BT) and control (CT) groups. 201,326 potential splicing junctions detected were supported by ≥3 junction reads. Approximately 94% of these junctions conformed to the consensus sequence (GT/AG) while ∼3% were GC/AG junctions. No AT/AC junctions were observed. A total of 2,834 exon skipping events, supported by a minimum of 3 junction reads, were detected. At least 7 genes, their mRNA expression significantly affected by butyrate, also had exon skipping events differentially regulated by butyrate. Furthermore, COL5A3, which was induced 310-fold by butyrate (FDR <0.001) at the gene level, had a significantly higher number of junction reads mapped to Exon#8 (Donor) and Exon#11 (Acceptor) in BT. This event had the potential to result in the formation of a COL5A3 mRNA isoform with 2 of the 69 exons missing. In addition, 216 differentially expressed transcript isoforms regulated by butyrate were detected. For example, Isoform 1 of ORC1 was strongly repressed by butyrate while Isoform 2 remained unchanged. Butyrate physically binds to and inhibits all zinc-dependent HDACs except HDAC6 and HDAC10. Our results provided evidence that butyrate also regulated deacetylase activities of classical HDACs via its transcriptional control. Moreover, thirteen gene fusion events differentially affected by butyrate were identified. Our results provided a snapshot into complex transcriptome dynamics regulated by butyrate, which will facilitate our understanding of the biological effects of butyrate and other HDAC inhibitors.
登录
查看更多内容
在眼中禁止作为氧化应激生物标志物。
DOI：
10.1016/j.ijbiomac.2010.08.018
发表时间：
2010-12-01
影响因子：
8.2
作者：
Lee H;Arnouk H;Sripathi S;Chen P;Zhang R;Bartoli M;Hunt RC;Hrushesky WJ;Chung H;Lee SH;Jahng WJ
通讯作者：
Jahng WJ
影响因子：
48
作者：
Katz, Yarden;Wang, Eric T.;Airoldi, Edoardo M.;Burge, Christopher B.
通讯作者：
Burge, Christopher B.
影响因子：
7
作者：
Akiva, P;Toporik, A;Sorek, R
通讯作者：
Sorek, R
鲍马斯转录组的表征是牛对胃肠道线虫的抗性机制。
影响因子：
4.4
作者：
Li RW;Rinaldi M;Capuco AV
通讯作者：
Capuco AV
影响因子：
5.6
作者：
Carafa V;Nebbioso A;Altucci L
通讯作者：
Altucci L