RNA‐Binding Proteins Shape Mammalian Retroelement RNA Fate: Lessons From HIV‐1, LINE‐1, and Related Reverse‐Transcribing Elements

ABSTRACT

Retroviruses and retrotransposons, collectively referred to here as retroelements, rely on reverse transcription for their propagation. These elements play important roles in viral infection, genome evolution, gene regulation, and disease. Human immunodeficiency virus type 1 (HIV‐1) and long interspersed nuclear element‐1 (LINE‐1) represent two well‐characterized systems, whereas endogenous retroviruses (ERVs) provide additional insights into the regulation of retroelement‐derived RNAs. Beyond element‐encoded proteins, host RNA‐binding proteins (RBPs) regulate multiple stages of retroelement RNA metabolism, including RNA processing, localization, translation, stability, and ribonucleoprotein (RNP) assembly, thereby influencing productive propagation or restriction. In this review, we use an RNP‐state framework to compare how RBPs and related RNA‐associated factors regulate HIV‐1 and LINE‐1, from early RNA processing and RNP assembly to reverse transcription, innate immune sensing, nuclear trafficking, and genome integration or insertion. We also incorporate evidence from ERVs and other retroviral systems, including human T‐cell leukemia virus type 1 (HTLV‐1), Moloney murine leukemia virus (MLV), and foamy viruses. Finally, we discuss experimental approaches for investigating RBP–retroelement interactions and highlight outstanding questions concerning RBP specificity, biomolecular condensates, context‐dependent regulation, evolutionary conservation, and potential therapeutic applications.