Leung Euphemia, Hong Jiwon, Fraser Alan, Krissansen Geoffrey W
Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Mol Immunol. 2007 Jan;44(4):284-94. doi: 10.1016/j.molimm.2006.03.009. Epub 2006 May 3.
Mutated variants of NOD2, a cytosolic Toll-like receptor (TLR) that recognizes bacterial peptidoglycan, are responsible for increased susceptibility to Crohn's disease (CD). TLRs and their related plant counterparts, the disease-resistance R proteins, undergo alternative splicing as a means of controlling activity. Here we report that regions of NOD2 RNA transcripts that encode the N-terminal and leucine-rich repeat (LRR) domains are alternatively spliced, potentially creating at least eight putative NOD2 variants. The most common variant is a short truncated isoform designated NOD2-short which terminates at residue position 820 leaving three LRR domains. An N-terminally spliced variant designated NOD2-190 contains only CARD1 and a partial CARD2 domain. The expression of transcripts encoding full-length and alternatively spliced forms of NOD2 was altered in blood mononuclear cells and monocytic cell lines stimulated by bacterial products. NOD2-short and NOD2-190 were inactive and unresponsive to muramyl dipeptide (MDP), but did not antagonize the activity of wild-type NOD2. Alternative splicing of NOD2 transcripts represents a potential mechanism by which the intracellular bacterial sensing activity of NOD2 is altered or down-regulated.
NOD2是一种可识别细菌肽聚糖的胞质Toll样受体（TLR），其突变变体与克罗恩病（CD）易感性增加有关。TLR及其相关的植物对应物——抗病R蛋白，会通过可变剪接来控制活性。在此，我们报告称，编码NOD2 N端和富含亮氨酸重复序列（LRR）结构域的RNA转录区域会发生可变剪接，可能产生至少8种假定的NOD2变体。最常见的变体是一种短截短异构体，命名为NOD2-short，在第820位残基处终止，仅留下3个LRR结构域。一种N端剪接变体命名为NOD2-190，仅包含CARD1和部分CARD2结构域。在细菌产物刺激的血液单核细胞和单核细胞系中，编码NOD2全长和可变剪接形式的转录本表达发生改变。NOD2-short和NOD2-190无活性，对胞壁酰二肽（MDP）无反应，但不拮抗野生型NOD2的活性。NOD2转录本的可变剪接代表了一种潜在机制，通过该机制，NOD2的细胞内细菌感应活性会发生改变或下调。
