The nucleic acid data:
IRESite Id: 57 Version: 8
Originaly submitted by: Václav Vopálenský Submission date: 2006-01-12 00:00:00
Reviewed by: Martin Mokrejš Last change: 2010-11-30 21:33:39
IRESite record type:
  natural_transcript
The shape of the nucleic acid molecule translated:
  linear
The quality of the mRNA/+RNA sequence:
  5UTR_possibly_incomplete
The abbreviated name of the virus/gene coding for this mRNA/+RNA molecule:
  AML1/RUNX1
The genetic origin of this natural mRNA/+RNA:
  nuclear
The GenBankId GI:# number of exactly this mRNA/+RNA sequence:
49574545
Synonyms of the gene name:
Synonym: AML1
Synonym: CBFA2
Synonym: EVI-1
Synonym: AMLCR1
Synonym: PEBP2A2
Synonym: PEBP2aB
Synonym: AML1-EVI-1
The mRNA/+RNA description: 
Homo sapiens runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) (RUNX1), transcript
variant 2, mRNA. Poly(A)-tail sequence dropped.
The mRNA/+RNA sequence represented in the +DNA notation:


Credibility of mRNA sequence:
  guessed_as_the_sequence_was_never_published_by_authors_nor_described_in_sufficient_detail
The organism containing this mRNA with IRES segment in its genome:
Homo sapiens
A promoter reported in cDNA corresponding to IRES sequence:
  not tested
The total number of notable open-reading frames (ORFs):
  1
Notable Open-Reading Frames (ORFs; protein coding regions) in the mRNA/+RNA sequence:
ORF
ORF position:   1
Version: 2 Last change: 2009-09-01 17:37:18
Originaly submitted by: Václav Vopálenský Reviewed by: Martin Mokrejš
The abbreviated name of this ORF/gene:
RUNX1
The description of the protein encoded in this ORF:
runt-related transcription factor 1 isoform b
The translational frameshift (ribosome slippage) involved:
  0
The ribosome read-through involved:
  no
The alternative forms of this protein occur by the alternative initiation of translation:
  no
The ORF absolute position (the base range includes START and STOP codons or their equivalents):
  1579-2940
Remarks:
Expression of AML1/RUNX1 is regulated at the level of transcription by two promoters distal (D) and proximal
(P) located about 150kb apart. While the transcripts with shorter (452b) D-UTR (6 kb in total) are efficiently
translated by cap-dependent translation (95% compared to CAT 5'-UTR and reverse-oriented D-UTR in
monocistronic assay), the longer P-UTR variant (1631b) transcripts (3, 4 and 8 kb in total) are poorly
translated (31% compared to CAT 5'-UTR) and translation initiation is mediated by a cap-independent
translation through IRES.
The P-UTR (1631b) is from a single exon and contains 15 uAUG codons and two GC-rich islands. The D-UTR (452b)
is spliced from 4 exons and the protein encoded is longer by 32 aminoacids at its N-terminus in contrast to
the proteins encoded by 4 and 8kb mRNAs. It depends on the cell line whether the trancripts with longer or
shorter 5'-UTR are more abundant (which reflects activity of the proximal or distal promoter). It seems both
promoters are active simultaneously, although to various extent.

AML/RUNX genes (previously termed CBFA or PEBP2alpha) belong to a family of heterodimeric transcription
factors having 128aa runt domain (RD), because of its homology to Drosophila Runt protein. AML1/RUNX1 and
AML3/RUNX2 play crucial role in hematopoiesis in mice while AML3/RUNX2 is essential for osteoporesis.

5'-UTR is incomplete, according to the article should have 1631b instead of only 1578 available here
(GI:966996).
P-UTR contains UUUCC sequence in its 3' part and complementary to the 3' end of 18S rRNA and further it
contains internal oligopyrimidine tract.

AML1 IRES was studied using capped T7 transcripts in Rabbit Reticulocyte Lysates and their translation was
resistant to pretreatment (30 min) of RRL by picornaviral 2A protease cleaving eIF4G protein.

Integrity of the transcripts was verified by Northern blot utilising 590b long probe against 5' part of the
second cistron (LUC) of BAP plasmid.
Citations:
Pozner A., Goldenberg D., Negreanu V., Le S. Y., Elroy-Stein O., Levanon D., Groner Y. (2000) Transcription-coupled translation control of AML1/RUNX1 is mediated by cap- and internal ribosome entry site-dependent mechanisms. Mol. Cell. Biol. 20(7):2297-2307
Bee T, Ashley EL, Bickley SR, Jarratt A, Li PS, Sloane-Stanley J, Göttgens B, de Bruijn MF (2009) The mouse Runx1 +23 hematopoietic stem cell enhancer confers hematopoietic specificity to both Runx1 promoters. Blood. 113(21):5121-5124
IRESs:
IRES:
Version: 3 Last change: 2007-01-19 00:00:00
Originaly submitted by: Václav Vopálenský Reviewed by: Martin Mokrejš
The IRES name:
  AML1/RUNX1
The IRES absolute position (the range includes START and STOP codons or their equivalents):
  39-1599
Conclusion:
  putative_IRES
How IRES boundaries were determined:
guessed
The sequence of IRES region aligned to its secondary structure (if available):


Remarks:
Part of the AML1/RUNX1 5' UTR (nt 39 to nt 1578) and the first 21 nt from ORF.
Citations:
Pozner A., Goldenberg D., Negreanu V., Le S. Y., Elroy-Stein O., Levanon D., Groner Y. (2000) Transcription-coupled translation control of AML1/RUNX1 is mediated by cap- and internal ribosome entry site-dependent mechanisms. Mol. Cell. Biol. 20(7):2297-2307
Last change to the database: 2015-04-16 16:45:23 GMT+1