Introns regulate gene expression in Cryptococcus neoformans in a Pab2p dependent pathway.
Introns regulate gene expression in Cryptococcus neoformans in a Pab2p dependent pathway.
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DOI：
10.1371/journal.pgen.1003686
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Janbon G
中科院分区：
文献类型：
--
作者：
Goebels C;Thonn A;Gonzalez-Hilarion S;Rolland O;Moyrand F;Beilharz TH;Janbon G
大多数新生隐球菌的基因都被内含子打断，并且经常发生选择性剪接。在这项研究中，我们研究了内含子对新生葡萄球菌基因表达的影响。对于大多数被测试的基因，内含子的消除大大减少了信使核糖核酸的积累。值得注意的是，内含子的数量和位置以累积的方式调节基因的表达水平。对能够表达无内含子等位基因的突变菌株的筛选表明，核多聚(A)结合蛋白Pab2调节新生隐球菌基因表达的内含子依赖性调节。PAB2缺失部分恢复了无内含子mRNA的积聚。此外，我们的结果还表明，必需核酸酶Rrp44p和Xrn2p参与了新生隐形杆菌无内含子等位基因转录的mRNA的降解。双突变构建和过表达实验表明，Pab2p和Xrn2p可能作用于相同的途径，而Rrp44p似乎是独立作用的。最后，RRP6或CID14基因的缺失对无内含子等位基因的表达没有影响。RRP6基因和CID14基因分别编码核外体核酸酶和与TraMP复合体相关的聚(A)聚合酶。新生隐球菌是一种主要的人类病原体，导致免疫功能低下患者的致命感染。此前对其基因组的分析显示，其大部分基因都被内含子打断。在这里，我们证明了内含子以累积的方式调节基因的表达。我们还证明了内含子在这一过程中可以发挥积极的作用，也可以发挥消极的作用。我们发现了一种核多聚(A)结合蛋白(Pab2p)，它与新生葡萄球菌基因表达的内含子相关调控有关。我们还证明了基本核酸酶Rrp44p和Xrn2p参与了两条独立的途径，控制新生葡萄球菌基因表达的内含子依赖性调控。Xrn2p的调控似乎依赖于Pab2p，而Rrp44p则独立发挥作用。相反，另一个外体核酸酶Rrp6p和TRAMP相关的聚(A)聚合酶Cid14p似乎没有参与这一调控。我们的结果为真核生物中基因表达的调控提供了新的见解，更具体地说，为研究新生葡萄球菌的生物学和毒力提供了新的见解。
Most Cryptococccus neoformans genes are interrupted by introns, and alternative splicing occurs very often. In this study, we examined the influence of introns on C. neoformans gene expression. For most tested genes, elimination of introns greatly reduces mRNA accumulation. Strikingly, the number and the position of introns modulate the gene expression level in a cumulative manner. A screen for mutant strains able to express functionally an intronless allele revealed that the nuclear poly(A) binding protein Pab2 modulates intron-dependent regulation of gene expression in C. neoformans. PAB2 deletion partially restored accumulation of intronless mRNA. In addition, our results demonstrated that the essential nucleases Rrp44p and Xrn2p are implicated in the degradation of mRNA transcribed from an intronless allele in C. neoformans. Double mutant constructions and over-expression experiments suggested that Pab2p and Xrn2p could act in the same pathway whereas Rrp44p appears to act independently. Finally, deletion of the RRP6 or the CID14 gene, encoding the nuclear exosome nuclease and the TRAMP complex associated poly(A) polymerase, respectively, has no effect on intronless allele expression. Cryptococcus neoformans is a major human pathogen responsible for deadly infection in immunocompromised patients. The analysis of its genome previously revealed that most of its genes are interrupted by introns. Here, we demonstrate that introns modulate gene expression in a cumulative manner. We also demonstrate that introns can play a positive or a negative role in this process. We identify a nuclear poly(A) binding protein (Pab2p) as implicated in the intron-dependent control of gene expression in C. neoformans. We also demonstrate that the essential nucleases Rrp44p and Xrn2p are implicated in two independent pathways controlling the intron-dependent regulation of gene expression in C. neoformans. Xrn2p regulation seems to depend on Pab2p whereas Rrp44p acts independently. In contrast, the other exosome nuclease Rrp6p and the TRAMP associated poly(A) polymerase Cid14p do not appear to be implicated in this regulation. Our results provide new insights into the regulation of gene expression in eukaryotes and more specifically into the biology and virulence of C. neoformans.
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影响因子：
5.4
作者：
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作者：
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通讯作者：
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