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Article Dans Une Revue Nucleic Acids Research Année : 2022

Human histone pre-mRNA assembles histone or canonical mRNA-processing complexes by overlapping 3′-end sequence elements

Résumé

Abstract Human pre-mRNA processing relies on multi-subunit macromolecular complexes, which recognize specific RNA sequence elements essential for assembly and activity. Canonical pre-mRNA processing proceeds via the recognition of a polyadenylation signal (PAS) and a downstream sequence element (DSE), and produces polyadenylated mature mRNAs, while replication-dependent (RD) histone pre-mRNA processing requires association with a stem–loop (SL) motif and a histone downstream element (HDE), and produces cleaved but non-polyadenylated mature mRNAs. H2AC18 mRNA, a specific H2A RD histone pre-mRNA, can be processed to give either a non-polyadenylated mRNA, ending at the histone SL, or a polyadenylated mRNA. Here, we reveal how H2AC18 captures the two human pre-mRNA processing complexes in a mutually exclusive mode by overlapping a canonical PAS (AAUAAA) sequence element with a HDE. Disruption of the PAS sequence on H2AC18 pre-mRNA prevents recruitment of the canonical complex in vitro, without affecting the histone machinery. This shows how the relative position of cis-acting elements in histone pre-mRNAs allows the selective recruitment of distinct human pre-mRNA complexes, thereby expanding the capability to regulate 3′ processing and polyadenylation.

Dates et versions

hal-04065783 , version 1 (12-04-2023)

Identifiants

Citer

Francesco Ielasi, Sara Ternifi, Emeline Fontaine, Domenico Iuso, Yohann Couté, et al.. Human histone pre-mRNA assembles histone or canonical mRNA-processing complexes by overlapping 3′-end sequence elements. Nucleic Acids Research, 2022, 50 (21), pp.12425-12443. ⟨10.1093/nar/gkac878⟩. ⟨hal-04065783⟩
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