Gupta Aditi, Brown C Titus, Zheng Yong-Hui, Adami Christoph
Department of Microbiology and Molecular Genetics, Michigan State University, 567 Wilson Road, East Lansing, MI 48824, USA.
BEACON Center for the Study of Evolution in Action, Michigan State University, 567Wilson Road, East Lansing, MI 48824, USA.
Viruses. 2015 Sep 29;7(10):5191-205. doi: 10.3390/v7102869.
Not all pseudogenes are transcriptionally silent as previously thought. Pseudogene transcripts, although not translated, contribute to the non-coding RNA pool of the cell that regulates the expression of other genes. Pseudogene transcripts can also directly compete with the parent gene transcripts for mRNA stability and other cell factors, modulating their expression levels. Tissue-specific and cancer-specific differential expression of these "functional" pseudogenes has been reported. To ascertain potential pseudogene:gene interactions in HIV-1 infection, we analyzed transcriptomes from infected and uninfected T-cells and found that 21 pseudogenes are differentially expressed in HIV-1 infection. This is interesting because parent genes of one-third of these differentially-expressed pseudogenes are implicated in HIV-1 life cycle, and parent genes of half of these pseudogenes are involved in different viral infections. Our bioinformatics analysis identifies candidate pseudogene:gene interactions that may be of significance in HIV-1 infection. Experimental validation of these interactions would establish that retroviruses exploit this newly-discovered layer of host gene expression regulation for their own benefit.
并非所有假基因都如之前所认为的那样在转录上沉默。假基因转录本虽然不进行翻译,但会对细胞的非编码RNA库有贡献,而该RNA库可调节其他基因的表达。假基因转录本还能直接与亲本基因转录本竞争mRNA稳定性及其他细胞因子,从而调节它们的表达水平。已有报道称这些“功能性”假基因存在组织特异性和癌症特异性的差异表达。为了确定在HIV-1感染中潜在的假基因与基因的相互作用,我们分析了来自感染和未感染HIV-1的T细胞的转录组,发现有21个假基因在HIV-1感染中存在差异表达。这很有意思,因为这些差异表达的假基因中有三分之一的亲本基因与HIV-1生命周期有关,且这些假基因中有一半的亲本基因涉及不同的病毒感染。我们的生物信息学分析确定了可能在HIV-1感染中具有重要意义的候选假基因与基因的相互作用。对这些相互作用进行实验验证将证实逆转录病毒为自身利益利用了这一新发现的宿主基因表达调控层面。