Nucleic Acids Research, 1995, Vol. 23, No. 5 725-728
© 1995
SURVEY AND SUMMARY |
Multiple RNA binding domains (RBDs) just don't add up
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine 333, Cedar Street, New Haven, CT 06510-8024, USA 1Howard Hughes Medical Institute, Yale University School of Medicine 333, Cedar Street, New Haven, CT 06510-8024, USA
*To whom correspondence should be addressed
Received September 30, 1994. Revised January 5, 1995. Accepted January 5, 1995.
One of the most common motifs for binding RNA In eukaryotes is the RNA binding domain (RBD) or RNA Recognition Motif (RRM). One of the more intriguing aspects of these proteins Is their modular nature. Proteins have been found containing from one to four RRMs. In most instances, these domains have some basal level of non-sequence specific RNA binding affinity. In addition, many also have a higher affinity for a specific structure or sequence of RNA. In the cases of heterogenous nuclear ribonucleoprotein A1 (hnRNP A1), yeast poly-A binding protein and splicing factor U2AF65, the Individual free energy of binding of the RBDs for RNA are not strictly additive. By invoking a model in which the amino acids connecting adjoining RBDs are considered to be flexible linkers with an interresidue spacing of about 3.5 Å, it Is possible to predict the apparent association constants for at least some multl-RBD proteins to single-stranded RNA. We have surveyed the literature and found that individual RBDs are separated by linker sequences of highly variable length. These linkers provide a critical determinant of binding affinity and may modulate cis versus trans binding. A clearer understanding of multi-RBD binding is essential to critically evaluating the role of these proteins In RNA splicing, packaging and transport.
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