Thyroid hormone influences conditional transcript elongation of the apolipoprotein A-I gene in rat liver.
Chronic administration of thyroid hormone (T3) increases apoA-I gene expression in rat liver by enhancing mRNA maturation, but reduces apoA-I mRNA synthesis to 50% of control. To gain insight into the inverse relation of mRNA maturation and mRNA synthesis, we measured transcription in livers of control and T3-treated rats (50 micrograms/100 g body weight for 7 days) by nuclear run-on assays using overlapping antisense RNA probes encompassing the apoA-I gene. In control rats, after normalization for hybridization efficiency and probe length, the hybridization signals with intron 3 probes were reduced to 45% of those obtained with exon 1 to exon 3 probes (P < 0.01) indicating transcriptional arrest or pausing close to the exon 3-intron 3 border or 450 to 650 nucleotides downstream of the transcription start site. In T3-treated rats, the elongation block was nearly twice as effective, while the rate of transcription initiation was similar to control. In contrast, the distribution of nascent transcripts across the apoA-IV gene was symmetric, and T3-treatment suppressed apoA-IV mRNA synthesis by processes operating in the 5' region such as transcription initiation. Thus, conditional transcript elongation contributes to the regulation of apoA-I gene expression in rat liver.
Lin-Lee
Y C
YC
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Soyal
S M
SM
Surguchov
A
A
Sanders
S
S
Strobl
W
W
Patsch
W
W
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics*; D001054:Apolipoproteins A / Q000235:genetics; D001483:Base Sequence; D004247:DNA / Q000737:chemistry; D005091:Exons; D015870:Gene Expression / Q000187:drug effects*; D007438:Introns; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D015347:RNA Probes; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000494:pharmacology*
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D015347:RNA Probes; D016372:RNA, Antisense; D012333:RNA, Messenger; C022205:apolipoprotein A-IV; D014284:Triiodothyronine; D004247:DNA