Potato Spindle Tuber Viroid Modulates Its Replication through a Direct Interaction with a Splicing Regulator
Potato Spindle Tuber Viroid Modulates Its Replication through a Direct Interaction with a Splicing Regulator
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DOI：
10.1128/jvi.01004-18
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发表时间：
2018-10-01
影响因子：
5.4
通讯作者：
Wang, Ying
中科院分区：
文献类型：
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作者：
Jiang, Jian;Smith, Heather N.;Wang, Ying
类病毒是感染植物的环状非编码RNA(NcRNA)。尽管在遗传组成和生物发生方面有所不同，但类病毒和各种长的ncRNA都依赖于基于RNA结构的与细胞因子的相互作用来发挥功能。在细胞核中复制的类病毒利用DNA依赖的RNA聚合酶II进行转录，这一过程涉及一种独特的转录因子IIIA(TFIIIA-7ZF)的剪接形式。在这里，我们提供的证据表明，马铃薯纺锤体块茎类病毒(PSTVd)与TFIIIA剪接调节因子(核糖体蛋白L5[RPL5])在体外和体内相互作用。PSTVd感染削弱了RPL5对TFIIIA转录本剪接的调节作用，而RPL5的异位表达降低了TFIIIA-7ZF的表达，抑制了PSTVd的积累。此外，我们还证明了PSTVd基因组上的RPL5结合位点位于对复制至关重要的中央保守区。总而言之，我们的数据表明，类病毒可以调节自己的复制，并调节特定的调节因子，导致只有一个或几个基因的剪接变化。本研究还对了解ncRNAs的作用机制和阐明各种宿主-病原体相互作用中的全局剪接变化具有重要意义。类病毒是所有生物中最小的复制子。作为环状非编码RNA，类病毒可以在植物中复制和传播，通常会导致疾病症状。马铃薯纺锤型块茎类病毒(PSTVd)是核复制型类病毒的模式种，其繁殖需要转录因子IIIA(TFIIIA7ZF)的独特剪接形式。在这里，我们提供的证据表明，PSTVd直接与剪接调节因子RPL5相互作用，有利于TFIIIA-7ZF的表达，从而促进类病毒复制。这一发现为更好地理解类病毒生物学提供了新的见解，并揭示了基于非编码RNA的剪接调控。我们的发现也确立了RPL5是一种新的调节细胞核内类病毒复制的负面因子，并强调了一种潜在的类病毒控制手段。
Viroids are circular noncoding RNAs (ncRNAs) that infect plants. Despite differences in the genetic makeup and biogenesis, viroids and various long ncRNAs all rely on RNA structure-based interactions with cellular factors for function. Viroids replicating in the nucleus utilize DNA-dependent RNA polymerase II for transcription, a process that involves a unique splicing form of transcription factor IIIA (TFIIIA-7ZF). Here, we provide evidence showing that potato spindle tuber viroid (PSTVd) interacts with a TFIIIA splicing regulator (ribosomal protein L5 [RPL5]) in vitro and in vivo. PSTVd infection compromises the regulatory role of RPL5 over splicing of TFIIIA transcripts, while ectopic expression of RPL5 reduces TFIIIA-7ZF expression and attenuates PSTVd accumulation. Furthermore, we illustrate that the RPL5 binding site on the PSTVd genome resides in the central conserved region critical for replication. Together, our data suggest that viroids can regulate their own replication and modulate specific regulatory factors leading to splicing changes in only one or a few genes. This study also has implications for understanding the functional mechanisms of ncRNAs and elucidating the global splicing changes in various host-pathogen interactions.IMPORTANCE Viroids are the smallest replicons among all living entities. As circular noncoding RNAs, viroids can replicate and spread in plants, often resulting in disease symptoms. Potato spindle tuber viroid (PSTVd), the type species of nuclear-replicating viroids, requires a unique splicing form of transcription factor IIIA (TFIIIA7ZF) for its propagation. Here, we provide evidence showing that PSTVd directly interacts with a splicing regulator, RPL5, to favor the expression of TFIIIA-7ZF, thereby promoting viroid replication. This finding provides new insights to better understand viroid biology and sheds light on the noncoding RNA-based regulation of splicing. Our discovery also establishes RPL5 as a novel negative factor regulating viroid replication in the nucleus and highlights a potential means for viroid control.