Paralogs hnRNP L and hnRNP LL Exhibit Overlapping but Distinct RNA Binding Constraints |
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Authors: | Sarah A. Smith Debashish Ray Kate B. Cook Michael J. Mallory Timothy R. Hughes Kristen W. Lynch |
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Affiliation: | 1. Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.; 2. Donnelly Centre, University of Toronto, Toronto, Canada.; 3. Department of Molecular Genetics, University of Toronto, Toronto, Canada.; St Jude Children''s Research Hospital, United States of America, |
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Abstract: | HnRNP (heterogeneous nuclear ribonucleoprotein) proteins are a large family of RNA-binding proteins that regulate numerous aspects of RNA processing. Interestingly, several paralogous pairs of hnRNPs exist that exhibit similar RNA-binding specificity to one another, yet have non-redundant functional targets in vivo. In this study we systematically investigate the possibility that the paralogs hnRNP L and hnRNP LL have distinct RNA binding determinants that may underlie their lack of functional redundancy. Using a combination of RNAcompete and native gel analysis we find that while both hnRNP L and hnRNP LL preferentially bind sequences that contain repeated CA dinucleotides, these proteins differ in their requirement for the spacing of the CAs. Specifically, hnRNP LL has a more stringent requirement for a two nucleotide space between CA repeats than does hnRNP L, resulting in hnRNP L binding more promiscuously than does hnRNP LL. Importantly, this differential requirement for the spacing of CA dinucleotides explains the previously observed differences in the sensitivity of hnRNP L and LL to mutations within the CD45 gene. We suggest that overlapping but divergent RNA-binding preferences, as we show here for hnRNP L and hnRNP LL, may be commonplace among other hnRNP paralogs. |
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