RNA virus microRNA that mimics a B-cell oncomiR
RNA virus microRNA that mimics a B-cell oncomiR
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DOI：
10.1073/pnas.1116107109
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发表时间：
2012-02-21
影响因子：
11.1
通讯作者：
Sullivan, Christopher S.
中科院分区：
文献类型：
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作者：
Kincaid, Rodney P.;Burke, James M.;Sullivan, Christopher S.
微小RNA（microRNAs，miRNAs）是一类小分子RNA，在多种真核细胞过程中发挥调控作用。病毒编码的miRNAs引起了人们的极大兴趣，尽管大多数miRNAs的功能仍有待破译。迄今为止，仅从具有DNA基因组的病毒中鉴定出易于检测的、进化上保守的天然miRNA。结合大多数miRNA是由较长转录物的内切核酸裂解产生的事实，这一发现导致了一种普遍的概念，即天然存在的RNA病毒不会编码miRNA，以避免其基因组或mRNA的非生产性裂解。在这里，我们证明了牛白血病病毒（BLV），一种逆转录病毒的RNA基因组，编码一个保守的簇的miRNA，由RNA聚合酶III（pol III）转录。因此，BLV miRNA避免了基因组/mRNA切割的难题，因为只有亚基因组pol III转录物被有效地加工成miRNA。BLV感染与牛的B细胞肿瘤密切相关。由于BLV相关肿瘤中的大多数细胞表达很少的病毒mRNA或蛋白质，BLV如何促进肿瘤发生仍然是一个长达数十年的未解之谜。一种BLV miRNA BLV-miR-B4与宿主miRNA miR-29具有部分序列同一性和共同的靶点。由于miR-29过表达与类似于BLV相关肿瘤的B细胞肿瘤相关，我们的研究结果提示了BLV诱导肿瘤发生的可能机制。
MicroRNAs (miRNAs) are small RNAs that play a regulatory role in numerous and diverse eukaryotic cellular processes. Virus-encoded miRNAs have garnered much interest, although the functions of most remain to be deciphered. To date, readily detectable, evolutionarily conserved natural miRNAs have only been identified from viruses with DNA genomes. Combined with the fact that most miRNAs are generated from endonucleolytic cleavage of longer transcripts, this finding has led to a common conception that naturally occurring RNA viruses will not encode miRNAs to avoid unproductive cleavage of their genomes or mRNAs. Here we demonstrate that the bovine leukemia virus (BLV), a retrovirus with an RNA genome, encodes a conserved cluster of miRNAs that are transcribed by RNA polymerase III (pol III). Thus, the BLV miRNAs avoid the conundrum of genome/mRNA cleavage because only the subgenomic pol III transcripts are efficiently processed into miRNAs. BLV infection is strongly associated with B-cell tumors in cattle. Because most cells in BLV-associated tumors express little viral mRNAs or proteins, exactly how BLV contributes to tumorigenesis has remained a decades-long unsolved mystery. One BLV miRNA, BLV-miR-B4, shares partial sequence identity and shared common targets with the host miRNA, miR-29. As miR-29 overexpression is associated with B-cell neoplasms that resemble BLV-associated tumors, our findings suggest a possible mechanism contributing to BLV-induced tumorigenesis.