A common RNA structural motif involved in the internal initiation of translation of cellular mRNAs.
The 5'-non-translated regions (5'NTR) of human immunoglobulin heavy chain binding protein (BiP), Antennapedia (Antp) ofDrosophilaand human fibroblast growth factor 2 (FGF-2) mRNAs are reported to mediate translation initiation by an internal ribosome binding mechanism. In this study, we investigate predicted features of the higher order structures folded in these 5'NTR sequences. Statistical analyses of RNA folding detected a 92 nt unusual folding region (UFR) from 129 to 220, close to the initiator AUG in the BiP mRNA. Details of the structural analyses show that the UFR forms a Y-type stem-loop structure with an additional stem-loop in the 3'-end resembling the common structure core found in the internal ribosome entry site (IRES) elements of picornavirus. The Y-type structural motif is also conserved among a number of divergent BiP mRNAs. We also find two RNA elements in the 5'-leader sequence of human FGF-2. The first RNA element (96 nt) is 2 nt upstream of the first CUG start codon located in the reported IRES element of human FGF-2. The second (107 nt) is immediately upstream of the authentic initiator AUG of the main open reading frame. Intriguingly, the folded RNA structural motif in the two RNA elements is conserved in other members of FGF family and shares the same structural features as that found in the 5'NTR of divergent BiP mRNAs. We suggest that the common RNA structural motif conserved in the diverse BiP and FGF-2 mRNAs has a general function in the internal ribosome binding mechanism of cellular mRNAs.
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Laboratory of Mathematical Biology, Division of Basic Sciences, National Cancer Institute, NIH, Building 469, Room 151, Frederick, MD 21702, USA. shuyun@fcrfv1.ncifcrf.gov
Maizel
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JV
D051943:Antennapedia Homeodomain Protein; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence; D000091342:Endoplasmic Reticulum Chaperone BiP; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors
D051943:Antennapedia Homeodomain Protein; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018398:Homeodomain Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D005346:Fibroblast Growth Factors