Alternative splicing of the mRNA encoding the human cholesteryl ester transfer protein

Journal Article · Tue Mar 03 00:00:00 EST 1992 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00123a021· OSTI ID:5640462

Inazu, Akihiro; Quinet, E M; Wang, Suke; Brown, M L; Stevenson, S; Barr, M L; Moulin, P; Tall, A R ^[1]

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1. Columbia Univ., New York, NY (United States)

The plasma cholesteryl ester transfer protein (CETP) is known to facilitate the transfer of lipids between plasma lipoproteins. The human CETP gene is a complex locus encompassing 16 exons. The CETP mRNA is found in liver and small intestine as well as in a variety of peripheral tissues. While the CETP cDNA from human adipose tissue was being cloned, a variant CETP cDNA was discovered which excluded the complete sequence encoded by exon 9, but which was otherwise identical to the full-length CETP cDNA, suggesting modification of the CETP gene transcript by an alternative RNA splicing mechanism. RNase protection analysis of tissue RNA confirmed the presence of exon 9 deleted transcripts and showed that they represented a variable proportion of the total CETP mRNA in various human tissues including adipose tissue (25%), liver (33%), and spleen (46%). Transient expression of the exon 9 deleted cDNA in COS cells or stable expression in CHO cells showed that the protein encoded by the alternatively spliced transcript was inactive in neutral lipid transfer, smaller, and poorly secreted compared to the protein derived from the full-length cDNA. Endo H digestion suggested that the inactive, cell-associated protein was present within the endoplasmic reticulum. The experiments show that the expression of the human CETP gene is modified by alternative splicing of the ninth exon, in a tissue-specific fashion. The function of alternative splicing is unknown but could serve to produce a protein with a function other than plasma neutral lipid transfer, or as an on-off switch to regulate the local concentration of biologically active protein.

• OSTI ID: 5640462
• Journal Information: Biochemistry; (United States), Vol. 31:8, Issue 8; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GLYCOPROTEINS
TISSUE DISTRIBUTION
MESSENGER-RNA
MOLECULAR STRUCTURE
CHOLESTEROL
ENDOPLASMIC RETICULUM
LIPOPROTEINS
RECOMBINANT DNA
SPLEEN
BODY
CELL CONSTITUENTS
DISTRIBUTION
DNA
HYDROXY COMPOUNDS
LIPIDS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RNA
STEROIDS
STEROLS
550200* - Biochemistry