RNA-protein recognition

J.-M. Perez-Canadillas and G. Varani, Recent Advances in RNA-Protein Recognition , p. 53... 

WUhamson, J.R. Induced fit in RNA-protein recognition. Nature Structural Biology 7, 834-837, 2000. 

Hamy, F., et al. (1993). Hydrogen-bonding contacts in the major groove are required for human immunodeficiency virus type-1 tat protein recognition of TAR RNA. J. Mol. Biol. 230, 111-123. 

Over the past several years, combinatorial libraries of biological molecules, such as peptides and nucleic acids, have proven invaluable as reagents with which to study molecular recognition of proteins and non-proteins. Such libraries have been used extensively to define the specificity of protein/protein, protein/RNA, protein/peptide, and RNA/small molecule interactions. 

A small RNA molecule is an essential component of the signal-recognition particle, an RNA protein complex in the cytoplasm that helps target newly synthesized proteins to intracellular compartments and extracellular destinations. 

The bulged loops can either provide unique protein recognition sites by a direct interaction with the unpaired bases or by exposing the major groove at the termini of the adjacent helices. Moreover, a bulge may generate a bend in the RNA helix which can add to the specificity of a protein interaction. 

Since RNA double helices and most RNA/DNA hybrids have only been observed in conformations similar to the A-form [14-24] whereas studies of the DNA conformation in cells such as salmon sperm have revealed that the resting state of DNA appears to be the B-form [25], it is natural to speculate that the B-form is adopted for DNA replication whereas the A-form is adopted for transcription. Similar considerations apply in the case of synthetic polynucleotides a polynucleotide with a highly repetitive base sequence can be found in the S form under conditions in which a natural DNA with essentially random base sequence would be found in the B form. Highly repetitive sequences flanked on both sides by random sequences are known to exist in natural DNAs and so it is possible that under some ionic conditions the repetitive and random sequences would have different conformations. The potential to exploit such structural differences in control processes mediated by specific DNA-protein recognition mechanisms is clear. Although these speculations have not been confirmed, the fact that conformational transitions may be implicated in such fundamental biological processes is powerful justification for extensive study of the stereochemical pathways of these transitions and the factors which promote and control them. 

In contrast to the DNA interactions, RNAs differ from helical DNA in several ways that affect the possibilities for protein recognition (Draper, 1995) such as ... 

Flexible tertiary structures may link different parts of an RNA chain to create complex shapes for protein interactions As the consequence, RNA offers a richer diversity of hydrogen bondings, stacking configurations and geometries than DNA for protein recognition. 

Two well characterized internal loops that serve as protein recognition elements in an RNA mediated regulation are the Iron Responsive Element, IRE, found in the 5 -untranslated region (UTR) of ferritin mRNA and the 3 UTR of transferrin receptor mRNA and the Rev Response Element, RRE, found in the env gene of the HIV-1 retrovirus. These RNA elements are the binding sites of the IRP and Rev proteins respectively. 

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