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Updated: Apr 29, 2026

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
Published on: August 9, 2019
Climbing the vertebrate branch of U1A/U2B″ protein evolution
Kimberly J Delaney1, Sandra G Williams1, Mariah Lawler1
1Department of Biochemistry and Molecular Biophysics, Washington University Medical School, St. Louis, Missouri 63110, USA.
Abstract:
In the vertebrate lineage of the U1A/U2B″/SNF protein family, the U1A and U2B″ proteins bind to RNA stem-loops in the U1 or U2 snRNPs, respectively. However, their specialization is fairly recent, as they evolved from a single ancestral protein. The progress of their specialization (subfunctionalization) can be monitored by the amino acid sequence changes that give rise to their modern RNA-binding specificity. Using ancestral sequence reconstruction to predict the intermediates on the evolutionary branch, a probable path of sequential changes is defined for U1A and U2B″. The RNA-binding affinity for U1A/U2B″ protein ancestors was measured using modern U1 and U2 snRNA stem-loops and RNA stem-loop variants to understand how the proteins' RNA specificities evolved.
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