Suzuki Takashi, Swift Larry L
Department of Pathology, Microbiology and Immunology Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Research Service, Veterans Affairs, Tennessee Valley Health Care System, Nashville, TN, USA.
Sci Rep. 2016 Jun 3;6:27308. doi: 10.1038/srep27308.
Microsomal triglyceride transfer protein (MTP) is a unique lipid transfer protein essential for the assembly of triglyceride-rich lipoproteins by the liver and intestine. Previous studies in mice identified a splice variant of MTP with an alternate first exon. Splice variants of human MTP have not been reported. Using PCR approaches we have identified two splice variants in human tissues, which we have named MTP-B and MTP-C. MTP-B has a unique first exon (Ex1B) located 10.5 kb upstream of the first exon (Ex1A) for canonical MTP (MTP-A); MTP-C contains both first exons for MTP-A and MTP-B. MTP-B was found in a number of tissues, whereas MTP-C was prominent in brain and testis. MTP-B does not encode a protein; MTP-C encodes the same protein encoded by MTP-A, although MTP-C translation is strongly inhibited by regulatory elements within its 5'-UTR. Using luciferase assays, we demonstrate that the promoter region upstream of exon 1B is quite adequate to drive expression of MTP. We conclude that alternate splicing plays a key role in regulating cellular MTP levels by introducing distinct promoter regions and unique 5'-UTRs, which contain elements that alter translation efficiency, enabling the cell to optimize MTP activity.
微粒体甘油三酯转运蛋白（MTP）是一种独特的脂质转运蛋白，对肝脏和肠道组装富含甘油三酯的脂蛋白至关重要。先前在小鼠中的研究确定了MTP的一种剪接变体，其第一个外显子不同。尚未报道人类MTP的剪接变体。我们使用PCR方法在人体组织中鉴定出两种剪接变体，我们将其命名为MTP-B和MTP-C。MTP-B有一个独特的第一个外显子（Ex1B），位于经典MTP（MTP-A）的第一个外显子（Ex1A）上游10.5 kb处；MTP-C包含MTP-A和MTP-B的两个第一个外显子。在许多组织中发现了MTP-B，而MTP-C在脑和睾丸中很突出。MTP-B不编码蛋白质；MTP-C编码与MTP-A相同的蛋白质，尽管MTP-C的翻译受到其5'-UTR内调控元件的强烈抑制。使用荧光素酶测定法，我们证明外显子1B上游的启动子区域足以驱动MTP的表达。我们得出结论，可变剪接通过引入不同的启动子区域和独特的5'-UTR在调节细胞MTP水平中起关键作用，这些5'-UTR包含改变翻译效率的元件，使细胞能够优化MTP活性。
