Tsurushita N, Ho L, Korn L J
Department of Genetics, Stanford University School of Medicine, CA 94305.
Science. 1988 Jan 29;239(4839):494-7. doi: 10.1126/science.3124268.
Regulation of the synthesis of membrane-bound and secreted immunoglobulin mu heavy chains at the level of RNA processing is an important element for B cell development. The precursor mu RNA is either polyadenylated at the upstream poly(A) site (for the secreted form) or spliced (for the membrane-bound form) in a mutually exclusive manner. When the mouse mu gene linked to the SV40/HSV-TK hybrid promoter was microinjected into Xenopus oocytes, the mu messenger RNA (mRNA) was altered by coinjection of nuclei of mouse surface IgM-bearing B-lymphoma cells to include the synthesis of the membrane-bound form. An increase in the membrane-bound form was not observed when nuclei of IgM-secreting hybridoma cells or fibroblast cells were coinjected. Deletion of the upstream poly(A) site did not eliminate the effect of B-lymphoma nuclei suggesting that membrane-specific splicing is stimulated. Further, splicing of other mu gene introns was not affected by coinjection of B-lymphoma nuclei. These results suggest that mature B cells contain one or more transacting nuclear factors that stimulate splicing specific for membrane-bound mu mRNA.
在RNA加工水平上对膜结合型和分泌型免疫球蛋白μ重链合成的调控是B细胞发育的一个重要因素。前体μRNA要么在上游聚腺苷酸化位点进行聚腺苷酸化（用于分泌形式），要么以互斥的方式进行剪接（用于膜结合形式）。当将与SV40/HSV-TK杂交启动子相连的小鼠μ基因显微注射到非洲爪蟾卵母细胞中时，通过共注射携带小鼠表面IgM的B淋巴瘤细胞核，μ信使RNA（mRNA）发生改变，从而包括膜结合形式的合成。当共注射IgM分泌型杂交瘤细胞或成纤维细胞的细胞核时，未观察到膜结合形式的增加。上游聚腺苷酸化位点的缺失并未消除B淋巴瘤细胞核的作用，这表明膜特异性剪接受到刺激。此外，其他μ基因内含子的剪接不受B淋巴瘤细胞核共注射的影响。这些结果表明，成熟B细胞含有一种或多种反式作用核因子，可刺激膜结合型μmRNA的特异性剪接。
