Detained introns are a novel, widespread class of post-transcriptionally spliced introns.
Detained introns are a novel, widespread class of post-transcriptionally spliced introns.
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DOI：
10.1101/gad.247361.114
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发表时间：
2015-01-01
影响因子：
10.5
通讯作者：
Sharp PA
中科院分区：
文献类型：
--
作者：
Boutz PL;Bhutkar A;Sharp PA
胚胎干细胞RNA的深度测序揭示了许多特定的内部内含子，这些内含子在多腺苷化的转录本中明显比其他内含子丰富。Boutz等人。在人类和小鼠细胞系以及成年小鼠肝脏中发现了数千个这样的“滞留”内含子(Dis)。药物抑制CLK--一种压力反应激酶--会引发特定dis子集的快速剪接变化，从而改变>；300基因的转录库。Srsf4调控一些dis的剪接，特别是在编码RNA加工和剪接因子的基因中。对胚胎干细胞RNA的深度测序揭示了许多特定的内部内含子，这些内含子在多腺化转录本中比其他内含子要丰富得多；我们将这些内含子归类为“滞留”内含子(Dis)。我们在人类和小鼠细胞系以及成年小鼠肝脏中发现了数千种dis，其中许多在进化上是保守的。DIS的半衰期可以超过一个小时，但仍然留在原子核中，不会受到无意义介导的衰变(NMD)的影响。抑制CLK--一种压力反应激酶--的药物，引发了特定dis亚群的快速剪接变化；一半表现为剪接增加，另一半表现为内含子滞留增加，改变了>；300基因的转录库。在CLK激酶抑制后，Srsf4经历了戏剧性的磷酸化变化，调节了一些异构体的剪接，特别是在编码RNA加工和剪接因子的基因中。DNA损伤后，一些dis的剪接--包括p53的负调控因子mdm4中的dis--的剪接也发生了变化。在CLK抑制4h后，>；400基因的表达发生了显著变化，其中几乎三分之一是P53转录靶点。这些数据表明，dis的剪接率对基因表达水平的影响是一种广泛存在的机制。
Deep sequencing of embryonic stem cell RNA revealed many specific internal introns that are significantly more abundant than the other introns within polyadenylated transcripts. Boutz et al. identified thousands of these “detained” introns (DIs) in human and mouse cell lines as well as the adult mouse liver. Drug inhibition of Clk, a stress-responsive kinase, triggered rapid splicing changes for a specific subset of DIs, altering transcript pools of >300 genes. Srsf4 regulates the splicing of some DIs, particularly in genes encoding RNA processing and splicing factors. Deep sequencing of embryonic stem cell RNA revealed many specific internal introns that are significantly more abundant than the other introns within polyadenylated transcripts; we classified these as “detained” introns (DIs). We identified thousands of DIs, many of which are evolutionarily conserved, in human and mouse cell lines as well as the adult mouse liver. DIs can have half-lives of over an hour yet remain in the nucleus and are not subject to nonsense-mediated decay (NMD). Drug inhibition of Clk, a stress-responsive kinase, triggered rapid splicing changes for a specific subset of DIs; half showed increased splicing, and half showed increased intron detention, altering transcript pools of >300 genes. Srsf4, which undergoes a dramatic phosphorylation shift in response to Clk kinase inhibition, regulates the splicing of some DIs, particularly in genes encoding RNA processing and splicing factors. The splicing of some DIs—including those in Mdm4, a negative regulator of p53—was also altered following DNA damage. After 4 h of Clk inhibition, the expression of >400 genes changed significantly, and almost one-third of these are p53 transcriptional targets. These data suggest a widespread mechanism by which the rate of splicing of DIs contributes to the level of gene expression.
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影响因子：
64.5
作者：
Bhatt DM;Pandya-Jones A;Tong AJ;Barozzi I;Lissner MM;Natoli G;Black DL;Smale ST
通讯作者：
Smale ST
DOI：
10.1073/pnas.1017700108
发表时间：
2011-05-17
影响因子：
11.1
作者：
Cho, Suhyung;Hoang, Amy;Ghosh, Gourisankar
通讯作者：
Ghosh, Gourisankar
影响因子：
8
作者：
Allende-Vega, N.;Dayal, S.;Saville, M. K.
通讯作者：
Saville, M. K.
影响因子：
7
作者：
Braunschweig U;Barbosa-Morais NL;Pan Q;Nachman EN;Alipanahi B;Gonatopoulos-Pournatzis T;Frey B;Irimia M;Blencowe BJ
通讯作者：
Blencowe BJ
影响因子：
--
作者：
Fedorov O;Huber K;Eisenreich A;Filippakopoulos P;King O;Bullock AN;Szklarczyk D;Jensen LJ;Fabbro D;Trappe J;Rauch U;Bracher F;Knapp S
通讯作者：
Knapp S