Definition: Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
Input: The expression of selenoproteins requires the translational recoding of the UGA stop codon to selenocysteine. In eukaryotes, this requires an RNA stem loop structure in the 3'-untranslated region, termed a selenocysteine insertion sequence (SECIS), and SECIS-binding protein 2 (SBP2). This study implicates SBP2 in dictating the hierarchy of selenoprotein expression, because it is the first to show that SBP2 distinguishes between SECIS elements in vitro. Using RNA electrophoretic mobility shift assays, we demonstrate that a naturally occurring mutation in SBP2, which correlates with abnormal thyroid hormone function in humans, lies within a novel, bipartite RNA-binding domain. This mutation alters the RNA binding affinity of SBP2 such that it no longer stably interacts with a subset of SECIS elements. Assays performed under competitive conditions to mimic intracellular conditions suggest that the differential affinity of SBP2 for various SECIS elements will determine the expression pattern of the selenoproteome. We hypothesize that the selective loss of a subset of selenoproteins, including some involved in thyroid hormone homeostasis, is responsible for the abnormal thyroid hormone metabolism previously observed in the affected individuals.
