Genomic Accumulation of Retrotransposons Was Facilitated by Repressive RNA‐Binding Proteins: A Hypothesis

RNA‐binding proteins (RBPs) regulate retrotransposition, and often also recognize and bind to retrotransposon‐derived elements (RDEs) in introns to regulate the effects of RDEs on pre‐mRNA processing. This integrated view proposes a role for RBPs in explaining how mammalian genomes accommodate vast numbers of RDEs, and suggests new avenues for understanding RBP:RDE biology.

Retrotransposon‐derived elements (RDEs) can disrupt gene expression, but are nevertheless widespread in metazoan genomes. This review presents a hypothesis that repressive RNA‐binding proteins (RBPs) facilitated the large‐scale accumulation of RDEs. Many RBPs bind RDEs in pre‐mRNAs to repress the effects of RDEs on RNA processing, or the formation of inverted repeat RNA structures. RDE‐binding RBPs often assemble on extended, multivalent binding sites across the RDE, which ensures repression of cryptic splice or polyA sites. RBPs thereby minimize the effects of RDEs on gene expression, which likely reduces the negative selection against RDEs. While mutations that change splice sites in RDEs act as an off‐on switch in exon formation, mutations that decrease the multivalency of RBP binding sites resemble a rheostat that enables a more gradual evolution of new RDE‐derived exons. RBPs might also repress aberrant processing of active retrotransposons, thus increasing the chance that full‐length copies are made. Taken together, in this review, it is proposed that RBPs facilitate the widespread accumulation of intronic RDEs by repressing RNA processing while chaperoning their potential to gradually evolve into new exons.

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