The nucleic acid data:
IRESite Id: 259 Version: 13
Originaly submitted by: Martin Mokrejš
Reviewed by: Martin Mokrejš Last change: 2009-09-01 21:34:55
IRESite record type:
  natural_transcript
The shape of the nucleic acid molecule translated:
  linear
The quality of the mRNA/+RNA sequence:
  hopefully_full-length_mRNA
The abbreviated name of the virus/gene coding for this mRNA/+RNA molecule:
  c-IAP1
The genetic origin of this natural mRNA/+RNA:
  nuclear
The GenBankId GI:# number of exactly this mRNA/+RNA sequence:
41349435
Synonyms of the gene name:
Synonym: API1
Synonym: MIHB
Synonym: HIAP2
Synonym: RNF48
Synonym: cIAP1
Synonym: Hiap-2
Synonym: c-IAP1
Synonym: BIRC2
The mRNA/+RNA description: 
Homo sapiens baculoviral IAP repeat-containing 2 (BIRC2), mRNA. Poly(A)-tail was dropped from the sequence.
The mRNA/+RNA sequence represented in the +DNA notation:


Credibility of mRNA sequence:
  only_fragment_published_or_from_author_and_the_rest_is_a_guess
The organism containing this mRNA with IRES segment in its genome:
Homo sapiens
A promoter reported in cDNA corresponding to IRES sequence:
  no
The total number of notable open-reading frames (ORFs):
  1
Summary of possible issues when IRES cDNA is experimentally transcribed in vivo:
Summary of experiments studying integrity of the in vivo transcripts in a particular host:
Integrity (uniformity) of mRNA tested using Northern-blot:
homogeneous_population_of_molecules_confirmed
Integrity (uniformity) of mRNA tested using RNase protection:
not_tested
Integrity (uniformity) of mRNA tested using 5'-RACE:
not_tested
Integrity (uniformity) of mRNA tested using primer extension :
not_tested
Integrity (uniformity) of mRNA tested using RT-PCR:
heterogeneous_population_of_molecules_found
Integrity (uniformity) of mRNA tested using real-time quantitative polymerase chain reaction (rtqPCR):
not_tested
Integrity (uniformity) of mRNA tested using RNAi:
not_tested
Integrity (uniformity) of mRNA tested using S1 nuclease mapping:
not_tested
Cryptic promoter presence was confirmed by expression from a promoter-less plasmid:
no_promoter_confirmed
Cryptic promoter presence was confirmed in an experimental setup involving inducible promoter:
not_tested
Integrity (uniformity) of mRNA molecules or possible promoter presence expressed in vivo was tested using another method, please specify in Remarks:
not_tested
The organism used:
Homo sapiens HepG2 (ATCC HB-8065)
Notable Open-Reading Frames (ORFs; protein coding regions) in the mRNA/+RNA sequence:
ORF
ORF position:   1
Version: 0
Originaly submitted by: Martin Mokrejš Reviewed by: Martin Mokrejš
The abbreviated name of this ORF/gene:
BIRC2
The description of the protein encoded in this ORF:
baculoviral IAP repeat-containing protein 2
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:
  not tested
The ORF absolute position (the base range includes START and STOP codons or their equivalents):
  1400-3256
OPTIONAL: The function of the encoded protein
NFR2-TRAF signalling complex protein; apoptosis inhibitor 1
Remarks:
The cloned 5'-UTR by van Eden et al. (2004) region was not a complete 5'-UTR. There are 3 mutations in
the cloned sequence provided by R. Lloyd in comparison to both German and NIH cDNA projects: GI:34367137 and
GI:22382083. -297nt from initiator ATG is A instead of G, -177nt is A instead of T, -76nt is G instead of T.
The sequence provided to IRESite by R. Lloyd spans -1115 to +4 (while the +4 base not shown in van Eden
et al. (2004) Fig. 1A is 'G'. van Eden showed already published 5'-UTR of NM_001166.2 (GI:10880127) GenBank
record which is 1159b long whereas current,, updated record GI:41349435 (NM_001166.3) contains 1.4kb
untranslated region. Thus, the sequence presented here in IRESite is longer by 240 nt at the very 5'-end
compared to the sequence shown by van Eden in Figure 1.

It appears the ATG codons at positions 1400 and 1463 are in-frame. The TAA stop codon at postion 1453 of the
previously reported uORF (Lewis et al., (2005), Fig. 2) is not in-frame with the ATG codon and thus it appears
based on the current sequence that the uORF does not exist. As a consequence, the IRES reported by M. Holcik
group spans into the CDS region whereas the region studied by R. Lloyd group was within the 5'-UTR. BLASTN
search for ESTs returns matches which show the current sequence with no uORF is correct.

Aberrantly spliced mRNAs were detected by RT-PCR (van Eden et al. (2004) Fig. 4D) which were not detectable
by Northern blot. The splice junction was AAGAGAAAG/CTATCAAAC and the splice event removed part of the RLuc
and most of cIAP1 5'-UTR from the intercistronic region (only 26 bp remained immediately upstream of the
initiatior ATG codon). Similarly, monocistronic mRNAs containing the chimeric intron and the cIAP1 5'-UTR
spliced at the same position.

Possible presence of a cryptic promoter was studied in a promoter-less plasmid and only very weak FLuc
activity was detected (Fig. 4C). In contrast, the control pGL3-Basic vector also lacking an SV40 promoter
expressed much lower amount of FLuc activity.

IRES activity was confirmed by direct bicistronic mRNA transfection (Fig. 5) which was capped and
poly(A)-tailed.
Citations:
Van Eden M. E., Byrd M. P., Sherrill K. W., Lloyd R. E. (2004) Translation of cellular inhibitor of apoptosis protein 1 (c-IAP1) mRNA is IRES mediated and regulated during cell stress. RNA. 10(3):469-481
IRESs:
IRES:
Version: 5 Last change: 2008-06-27 21:36:06
Originaly submitted by: Martin Mokrejš Reviewed by: Martin Mokrejš
The IRES name:
  c-IAP1_285-1399
The IRES absolute position (the range includes START and STOP codons or their equivalents):
  285-1399
Conclusion:
  weakly_supported_IRES
How IRES boundaries were determined:
experimentally_determined
The sequence of IRES region aligned to its secondary structure (if available):


Remarks:
IRES activity measurable only in cells directly transfected by RNA was at the best comparable to the activity
of HCV IRES and about 2x the activity of negative control (capped and poly(A)-tailed RNAs). More importantly,
the Fluc/RLuc ratio values were around 0.08 so the IRES-driven expression was very low compared to the
cap-dependent initiation.
Citations:
Van Eden M. E., Byrd M. P., Sherrill K. W., Lloyd R. E. (2004) Translation of cellular inhibitor of apoptosis protein 1 (c-IAP1) mRNA is IRES mediated and regulated during cell stress. RNA. 10(3):469-481
IRES:
Version: 2 Last change: 2008-06-27 21:12:29
Originaly submitted by: Martin Mokrejš Reviewed by: Martin Mokrejš
The IRES name:
  c-IAP1_1313-1462
The IRES absolute position (the range includes START and STOP codons or their equivalents):
  1313-1462
Conclusion:
  weakly_supported_IRES
How IRES boundaries were determined:
experimentally_determined
The sequence of IRES region aligned to its secondary structure (if available):


Remarks:
The minimal IRES as determined by Warnakulasuriyarachchi et al. (2004).
Citations:
Warnakulasuriyarachchi D., Cerquozzi S., Cheung H. H., Holcik M. (2004) Translational induction of the inhibitor of apoptosis protein HIAP2 during endoplasmic reticulum stress attenuates cell death and is mediated via an inducible internal ribosome entry site element. J. Biol. Chem. 279(17):17148-17157
IRES trans-acting factor (ITAFS):
IRES trans-acting factor (ITAF):
Version: 0
Originaly submitted by: Martin Mokrejš Reviewed by: Martin Mokrejš
Type of the interaction between ITAF and the RNA subject to translation:
indirect_interaction
ITAF protein characteristics:
Version: 0
Originaly submitted by: Martin Mokrejš Reviewed by: Martin Mokrejš
ITAF abbreviated name:
p97/DAP5/NAT1
ITAF fullname:
p97/DAP5/NAT1
ITAF description (long):
p97/DAP5/NAT1 cleavage product p86 oe eIF4G, 86 kDa, RNA binding protein
3.1.2. Organisms or in vitro systems where this ITAF was functionally studied:
Organism or in vitro system where ITAF was shown:
Necessity of ITAF for translation in this particular organism or system:
stimulatory
Method used to demonstrate ITAF effect:
in_vivo
The organism where action of this ITAF was studied:
Homo sapiens HEK 293T/17 (ATCC CRL-11268)
Remarks:
In contrast, the p86 cleavage product of p97/DAP5/NAT1 does not affect XIAP IRES.
Citations:
Warnakulasuriyarachchi D., Cerquozzi S., Cheung H. H., Holcik M. (2004) Translational induction of the inhibitor of apoptosis protein HIAP2 during endoplasmic reticulum stress attenuates cell death and is mediated via an inducible internal ribosome entry site element. J. Biol. Chem. 279(17):17148-17157
Last change to the database: 2015-04-16 16:45:23 GMT+1