Young P J, Le T T, thi Man N, Burghes A H, Morris G E
MRIC Biochemistry Group, North East Wales Institute, Mold Road, Wrexham, LL11 2AW, United Kingdom.
Exp Cell Res. 2000 May 1;256(2):365-74. doi: 10.1006/excr.2000.4858.
The spinal muscular atrophy protein, SMN, is a cytoplasmic protein that is also found in distinct nuclear structures called "gems." Gems are closely associated with nuclear coiled bodies and both may have a direct role in snRNP maturation and pre-RNA splicing. There has been some controversy over whether gems and coiled bodies colocalize or form adjacent/independent structures in HeLa and other cultured cells. Using a new panel of antibodies against SMN and antibodies against coilin-p80, a systematic and quantitative study of adult differentiated tissues has shown that gems always colocalize with coiled bodies. In some tissues, a small proportion of coiled bodies (<10%) had no SMN, but independent or adjacent gems were not found. The most striking observation, however, was that many cell types appear to have neither gems nor coiled bodies (e.g., cardiac and smooth muscle, blood vessels, stomach, and spleen) and this expression pattern is conserved across human, rabbit, and pig species. This shows that assembly of distinct nuclear bodies is not essential for RNA splicing and supports the view that they may be storage sites for reserves of essential proteins and snRNPs. Overexpression of SMN in COS-7 cells produced supernumerary nuclear bodies, most of which also contained coilin-p80, confirming the close relationship between gems and coiled bodies. However, when SMN is reduced to very low levels in type I SMA fibroblasts, coiled bodies are still formed. Overall, the data suggest that gem/coiled body formation is not determined by high cytoplasmic SMN concentrations or high metabolic activity alone and that a differentiation-specific factor may control their formation.
脊髓性肌萎缩蛋白（SMN）是一种细胞质蛋白，也存在于被称为“宝石体”的独特核结构中。宝石体与核卷曲体密切相关，二者可能在小核核糖核蛋白（snRNP）成熟和前体RNA剪接中发挥直接作用。在HeLa细胞和其他培养细胞中，宝石体和卷曲体是共定位还是形成相邻/独立结构一直存在一些争议。使用一组新的抗SMN抗体和抗卷曲蛋白-p80抗体，对成年分化组织进行的系统定量研究表明，宝石体总是与卷曲体共定位。在某些组织中，一小部分卷曲体（<10%）没有SMN，但未发现独立或相邻的宝石体。然而，最引人注目的观察结果是，许多细胞类型似乎既没有宝石体也没有卷曲体（如心肌和平滑肌、血管、胃和脾脏），并且这种表达模式在人类、兔子和猪物种中是保守的。这表明不同核体的组装对于RNA剪接并非必不可少，并支持它们可能是必需蛋白质和snRNP储备储存位点的观点。在COS-7细胞中过表达SMN会产生多余的核体，其中大多数也含有卷曲蛋白-p80，证实了宝石体和卷曲体之间的密切关系。然而，当I型脊髓性肌萎缩症成纤维细胞中的SMN降至非常低的水平时，仍然会形成卷曲体。总体而言，数据表明宝石体/卷曲体的形成并非仅由高细胞质SMN浓度或高代谢活性决定，并且一个分化特异性因子可能控制它们的形成。
