ArticleMolecular and cellular biology2000
Negative and translation termination-dependent positive control of FLI-1 protein synthesis by conserved overlapping 5' upstream open reading frames in Fli-1 mRNA.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 45 citations in OpenAlex.
- The role of upstream open reading frames in translation regulation in the apicomplexan parasitesParasitology · 2021Review
- Complete motif analysis of sequence requirements for translation initiation at non-AUG start codons.Nucleic acids research · 2018Article
- Fli1 acts downstream of Etv2 to govern cell survival and vascular homeostasis via positive autoregulation.Circulation research · 2014Article
- Genome-wide search for novel human uORFs and N-terminal protein extensions using ribosomal footprinting.Genome research · 2012Article
- Synthesis of two SAPAP3 isoforms from a single mRNA is mediated via alternative translational initiation.Scientific reports · 2012Article
- Exploring the selective constraint on the sizes of insertions and deletions in 5' untranslated regions in mammals.BMC evolutionary biology · 2011Article
- A mutation in an alternative untranslated exon of hexokinase 1 associated with hereditary motor and sensory neuropathy -- Russe (HMSNR).European journal of human genetics : EJHG · 2009Article
- Article
- 5'-untranslated regions with multiple upstream AUG codons can support low-level translation via leaky scanning and reinitiation.Nucleic acids research · 2004Article
- Ribosomes stalling on uORF1 in the Xenopus Cx41 5' UTR inhibit downstream translation initiation.Nucleic acids research · 2003Article
- Functional cross-antagonism between transcription factors FLI-1 and EKLF.Molecular and cellular biology · 2003Article
- Review
- Control of eukaryotic protein synthesis by upstream open reading frames in the 5'-untranslated region of an mRNA.The Biochemical journal · 2002Review
- Physical evidence for distinct mechanisms of translational control by upstream open reading frames.The EMBO journal · 2001Article
- Biology of EWS/ETS fusions in Ewing's family tumors.Oncogene · 2001Review
- The Ets-transcription factor family in embryonic development: lessons from the amphibian and bird.Oncogene · 2000Review
- Review
- Upstream open reading frames as regulators of mRNA translation.Molecular and cellular biology · 2000Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proto-oncogene Fli-1 encodes a transcription factor of the ets family whose overexpression is associated with multiple virally induced leukemias in mouse, inhibits murine and avian erythroid cell differentiation, and induces drastic perturbations of early development in Xenopus. This study demonstrates the surprisingly sophisticated regulation of Fli-1 mRNA translation. We establish that two FLI-1 protein isoforms (of 51 and 48 kDa) detected by Western blotting in vivo are synthesized by alternative translation initiation through the use of two highly conserved in-frame initiation codons, AUG +1 and AUG +100. Furthermore, we show that the synthesis of these two FLI-1 isoforms is regulated by two short overlapping 5' upstream open reading frames (uORF) beginning at two highly conserved upstream initiation codons, AUG -41 and GUG -37, and terminating at two highly conserved stop codons, UGA +35 and UAA +15. The mutational analysis of these two 5' uORF revealed that each of them negatively regulates FLI-1 protein synthesis by precluding cap-dependent scanning to the 48- and 51-kDa AUG codons. Simultaneously, the translation termination of the two 5' uORF appears to enhance 48-kDa protein synthesis, by allowing downstream reinitiation at the 48-kDa AUG codon, and 51-kDa protein synthesis, by allowing scanning ribosomes to pile up and consequently allowing upstream initiation at the 51-kDa AUG codon. To our knowledge, this is the first example of a cellular mRNA displaying overlapping 5' uORF whose translation termination appears to be involved in the positive control of translation initiation at both downstream and upstream initiation codons.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.