Evolution of histone mRNA 3' end processing machinery in eukaryotes

Zhao, B., Bond, U. M., Ni Leathlobhair, M.

10.64898/2026.10.14.759114 · was preprinted

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Abstract

Replication-dependent histone mRNAs in metazoans terminate in a conserved 3' stem-loop (SL) recognized by stem-loop binding protein (SLBP) and processed by a specialized U7 snRNP-dependent cleavage machinery. Outside animals, the evolutionary history of this pathway remains poorly resolved, and fungi and most plants are widely thought to have lost SLBP-SL-dependent histone mRNA processing entirely. Here, we combine large-scale homology searches, structural and domain analyses, and genome-wide mapping of histone 3'-end features across eukaryotes to reconstruct the evolution of histone mRNA processing machinery. We show that SLBP, stem-loop motifs and multiple U7-associated factors are far more broadly distributed across eukaryotes than previously appreciated, revising earlier models of widespread loss outside metazoans. Contrary to prevailing views, early-diverging fungal lineages retain SLBP orthologs with conserved RNA-binding domains, stem-loop motifs and additional components of the canonical pathway. Across fungi, we identify a clade-wise shift from SL-associated processing features toward canonical polyadenylation-associated features. Early-diverging fungi retain noncanonical poly(A) polymerases alongside SLBP and stem-loop motifs despite sparse U7-associated machinery, consistent with a previously unrecognized intermediate state in histone mRNA 3'-end processing. Our results support a stepwise evolutionary transition from ancestral SLBP/stem-loop-associated histone mRNA processing to canonical polyadenylation and provide a revised framework for the evolution of histone mRNA 3'-end formation in eukaryotes.

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biorxiv v1 2026-10-16 source ↗

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