Identification of a Novel Transcript and Regulatory Mechanism for Microsomal Triglyceride Transfer Protein

PloS One
Takashi SuzukiLarry L Swift

Abstract

Microsomal triglyceride transfer protein (MTP) is essential for the assembly of triglyceride-rich apolipoprotein B-containing lipoproteins. Previous studies in our laboratory identified a novel splice variant of MTP in mice that we named MTP-B. MTP-B has a unique first exon (1B) located 2.7 kB upstream of the first exon (1A) for canonical MTP (MTP-A). The two mature isoforms, though nearly identical in sequence and function, have different tissue expression patterns. In this study we report the identification of a second MTP splice variant (MTP-C), which contains both exons 1B and 1A. MTP-C is expressed in all the tissues we tested. In cells transfected with MTP-C, protein expression was less than 15% of that found when the cells were transfected with MTP-A or MTP-B. In silico analysis of the 5'-UTR of MTP-C revealed seven ATGs upstream of the start site for MTP-A, which is the only viable start site in frame with the main coding sequence. One of those ATGs was located in the 5'-UTR for MTP-A. We generated reporter constructs in which the 5'-UTRs of MTP-A or MTP-C were inserted between an SV40 promoter and the coding sequence of the luciferase gene and transfected these constructs into HEK 293 cells. Luciferase activity was sig...Continue Reading

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Citations

Sep 13, 2017·Proceedings of the National Academy of Sciences of the United States of America·Sebastian ZeissigRichard S Blumberg
Sep 19, 2019·Journal of Molecular and Cellular Cardiology·Martina KlevstigJan Borén
Mar 6, 2021·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·Xianyuan ZengYilei Wang

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Methods Mentioned

BETA
lipidation
PCR
Electrophoresis
transfection
Assay

Software Mentioned

Quantity One

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