Eis Peggy S, Tam Wayne, Sun Liping, Chadburn Amy, Li Zongdong, Gomez Mario F, Lund Elsebet, Dahlberg James E
Department of Biomolecular Chemistry, University of Wisconsin Medical School, 1300 University Avenue, Madison, WI 53706, USA.
Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3627-32. doi: 10.1073/pnas.0500613102. Epub 2005 Feb 28.
We show that the microRNA miR-155 can be processed from sequences present in BIC RNA, a spliced and polyadenylated but non-protein-coding RNA that accumulates in lymphoma cells. The precursor of miR-155 is likely a transient spliced or unspliced nuclear BIC transcript rather than accumulated BIC RNA, which is primarily cytoplasmic. By using a sensitive and quantitative assay, we find that clinical isolates of several types of B cell lymphomas, including diffuse large B cell lymphoma (DLBCL), have 10- to 30-fold higher copy numbers of miR-155 than do normal circulating B cells. Similarly, the quantities of BIC RNA are elevated in lymphoma cells, but ratios of the amounts of the two RNAs are not constant, suggesting that the level of miR-155 is controlled by transcription and processing. Significantly higher levels of miR-155 are present in DLBCLs with an activated B cell phenotype than with the germinal center phenotype. Because patients with activated B cell-type DLBCL have a poorer clinical prognosis, quantification of this microRNA may be diagnostically useful.
我们发现，微小RNA miR-155可从BIC RNA中的序列加工而来，BIC RNA是一种经过剪接和聚腺苷酸化但不编码蛋白质的RNA，在淋巴瘤细胞中积累。miR-155的前体可能是一种短暂剪接或未剪接的核BIC转录本，而非主要存在于细胞质中的积累型BIC RNA。通过使用一种灵敏的定量检测方法，我们发现包括弥漫性大B细胞淋巴瘤（DLBCL）在内的几种B细胞淋巴瘤临床分离株中，miR-155的拷贝数比正常循环B细胞高10至30倍。同样，淋巴瘤细胞中BIC RNA的量也有所升高，但两种RNA的量的比值并不恒定，这表明miR-155的水平受转录和加工过程的控制。具有活化B细胞表型的DLBCL中miR-155的水平显著高于具有生发中心表型的DLBCL。由于活化B细胞型DLBCL患者的临床预后较差，对这种微小RNA进行定量可能具有诊断价值。
