Conserved Functions of LARP1 Proteins in Eukaryotes

La and La-related proteins (LARPs) are conserved RNA-binding proteins that share a characteristic La motif (LaM) and have important functions in RNA metabolism. Members of the LARP1 family bind a cohort of mRNAs encoding factors involved in the process of mRNA translation, including ribosomal protein mRNAs (RP mRNAs). These mRNAs can contain a sequence of 5-15 pyrimidines in their 5'UTRs, immediately following the m⁷G cap, and are named 5' terminal oligopyrimidine (5'TOP) mRNAs. The DM15 domain of human LARP1 has been suggested to specifically recognize this motif, thereby affecting 5'TOP mRNA translation and stability. However, the specific function of LARP1 in this context remains unclear. Intriguingly, the 5'TOP motif is not found in RP mRNAs in C. elegans and yeast, while LARP1 orthologs in some systems lack the characteristic DM15 domain, suggesting that essential functions of LARP1 family members may precede the emergence of the 5'TOP motif and the DM15. In this work, we review studies in humans and several model organisms where we draw parallels between reported RNA binding modes and functions of different LARP1 orthologs. We further present common themes and areas for further investigation. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.