The expression of essential selenoproteins during zebrafish development requires SECIS binding protein 2-like

Abstract

The dietary requirement for selenium is based on its incorporation into selenoproteins, which contain the amino acid selenocysteine (Sec). The Sec insertion sequence (SECIS) is an RNA structure found in the 3 UTR of all selenoprotein mRNAs, and it is required to convert in-frame UGA codons from termination to Sec-incorporating codons. There are two proteins that bind to SECIS elements, but only one, SECIS binding protein 2 (Sbp2), has been shown to be required for Sec incorporation. The Sbp2 paralogue, SECIS binding protein 2-like (Secisbp2l) is conserved in all vertebrates and shares many features with Sbp2, but its function is unknown. Here we set out to determine the relative roles of Sbp2 and Secisbp2l by introducing CRISPR mutations in both genes in zebrafish. By monitoring selenoprotein synthesis with 75Se labeling during embryogenesis, we found that sbp2-/- embryos still make a select subset of selenoproteins but secisbp2l-/- embryos retain the full complement. Abrogation of both genes completely prevents selenoprotein synthesis and juveniles die at 14 days post fertilization. Embryos lacking Sbp2 are sensitive to oxidative stress and express the stress marker vtg1. We propose a model where Secisbp2l is required to promote essential selenoprotein synthesis during stress.