Inhibition of tumorigenicity by the 5'-untranslated RNA of the human c-myc P0 transcript.

Activity of the independently regulated human c-myc P0 promoter has been associated with the undifferentiated status of leukemia cells as well as the hormone-independent proliferation of breast cancer cells. The P0 transcript is distinguished from the predominant P1 and P2 c-myc mRNAs by an approximately 639-nucleotide extension of the 5'-untranslated region. We hypothesized that this complex 5'-untranslated RNA sequence unique to the P0 transcript may contribute significantly to the composite regulation of the c-myc locus and that enforced intracellular synthesis of the isolated P0 5'-UTR, out of its native sequence context, might amplify or dominantly interfere with its normal regulatory function.

Evidence for differential ribonucleoprotein complex assembly in vitro on the 5'-untranslated region of the human IGF-IR transcript.

The type I insulin-like growth factor receptor (IGF-IR) plays a key role in the control of cellular proliferation and survival. The human IGF-IR transcript is characterized by an unusually long 1038 nucleotide 5'-untranslated region (5'-UTR). We hypothesized that the contribution of this complex 5'-untranslated RNA sequence to the post-transcriptional regulation of IGF-IR expression would involve a dynamic interplay between RNA structure and specific RNA-binding proteins.

The 5'-untranslated RNA of the human dhfr minor transcript alters transcription pre-initiation complex assembly at the major (core) promoter.

The human dhfr minor transcript is distinguished from the predominant dhfr mRNA by an approximately 400 nucleotide extension of the 5'-untranslated region, which corresponds to the major (core) promoter DNA (its template). Based on its unusual sequence composition, we hypothesized that the minor transcript 5'-UTR might be capable of altering transcription pre-initiation complex assembly at the core promoter, through direct interactions of the RNA with specific regulatory polypeptides or the promoter DNA itself. We found that the minor transcript 5'-UTR selectively sequesters transcription factor Sp3, and to a lesser extent Sp1, preventing their binding to the dhfr core promoter.