A dominant negative form of transcription activator mTFE3 created by differential splicing.
Transcription factor E3 (mTFE3) is a murine transcription activator that binds to the intronic enhancer of the immunoglobulin heavy chain gene. A naturally occurring splice product of mTFE3 messenger RNA (mRNA) lacked 105 nucleotides that encode an activation domain; both absolute and relative amounts of long and truncated mRNAs varied in different tissues. Cells were cotransfected with complementary DNAs that encoded the two mRNA forms in amounts that corresponded to the amounts of each mRNA found in different cells. Small changes in substoichiometric amounts of the truncated form of mRNA effected trans-dominant negative modulation of mTFE3 activity. These findings identify a function for differential splicing in the regulation of transcription factor activity.
Roman
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Department of Biological Chemistry, University of California, Los Angeles 90024.
Cohn
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Calame
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D051379:Mice; D008969:Molecular Sequence Data; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C069203:TFE3 protein, human; D014157:Transcription Factors