Packaging and reverse transcription of snRNAs by retroviruses may generate pseudogenes

Packaging and reverse transcription of snRNAs by retroviruses may generate pseudogenes
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DOI:
10.1261/rna.2150604
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发表时间:
2004-02-01
期刊:
RNA
影响因子:
4.5
通讯作者:
Beemon, KL
Beemon, KL
中科院分区:
生物学3区
文献类型:
--
作者:
Giles, KE;Caputi, M;Beemon, KL

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逆转录病毒在每个病毒颗粒中特异性地包装其RNA基因组的两个拷贝,沿着一些小的细胞RNA,包括tRNA和7S L RNA。我们在这里显示,劳斯肉瘤病毒(RSV)也包装U6 snRNA在每个病毒粒子约一个拷贝。此外,通过北方印迹法在纯化病毒中检测到痕量的U1和U2 snRNA。U6 snRNA与RSV 70 S基因组RNA二聚体在蔗糖梯度上共迁移。我们观察到U6 snRNA在内源性反应中的逆转录,其中RSV颗粒是逆转录酶和RNA底物的来源。这一发现使我们研究了哺乳动物基因组序列中snRNA假基因的存在。对人类、小鼠和大鼠基因组的调查揭示了大量的剪接体snRNA假基因。U6假基因最丰富,每个基因组中约有200个拷贝。在人类基因组中,67%的U6 snRNA假基因和大量其他snRNA假基因与LINE、SINE或逆转录病毒LTR重复序列相关。我们提出,snRNA在逆转录病毒颗粒中的包装导致它们在感染细胞中的逆转录和snRNA/病毒重组体整合到宿主基因组中。
Retroviruses specifically package two copies of their RNA genome in each viral particle, along with some small cellular RNAs, including tRNAs and 7S L RNA. We show here that Rous sarcoma virus (RSV) also packages U6 snRNA at approximately one copy per virion. in addition, trace amounts of U1 and U2 snRNAs were detected in purified virus by Northern blotting. U6 snRNA comigrated with the RSV 70S genomic RNA dimer on sucrose gradients. We observed reverse transcription of U6 snRNA in an endogenous reaction in which RSV particles were the source of both reverse transcriptase and RNA substrates. This finding led us to examine mammalian genomic sequences for the presence of snRNA pseudogenes. A survey of the human, mouse, and rat genomes revealed a high number of spliceosomal snRNA pseudogenes. U6 pseudogenes were the most abundant, with approximately 200 copies in each genome. In the human genome, 67% of U6 snRNA pseudogenes, and a significant number of the other snRNA pseudogenes, were associated with LINE, SINE, or retroviral LTR repeat sequences. We propose that the packaging of snRNAs in retroviral particles leads to their reverse transcription in an infected cell and the integration of snRNA/viral recombinants into the host genome.