Abstract:
:We have derived a secondary structure model for the c-myc internal ribosome entry segment (IRES) by using information from chemical probing of the c-myc IRES RNA to constrain structure prediction programs. Our data suggest that the IRES is modular in nature, and can be divided into two structural domains linked by a long unstructured region. Both domains are required for full IRES function. Domain 1 is a complex element that contains a GNNRA apical loop and an overlapping double pseudoknot motif that is topologically unique amongst published RNA structures. Domain 2, the smaller of the two, contains an apical AUUU loop. We have located the ribosome landing site and have shown that ribosomes enter in a 16 nt region downstream of the pseudoknots in a situation similar to that observed in several viral IRESs. To test the structure, several key regions of the IRES were mutated and, interestingly, it appears that some of the structural elements that we have identified function to repress c-myc IRES function. This has profound implications for de-regulation of c-myc expression by mutations occurring in the IRES.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Le Quesne JP,Stoneley M,Fraser GA,Willis AEdoi
10.1006/jmbi.2001.4745keywords:
subject
Has Abstractpub_date
2001-06-29 00:00:00pages
111-26issue
1eissn
0022-2836issn
1089-8638pii
S0022-2836(01)94745-Xjournal_volume
310pub_type
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