Human histone pre-mRNA assembles histone or canonical mRNA-processing complexes by overlapping 3′-end sequence elements. Issue 21 (30th November 2022)

• Record Type: Journal Article
• Authors: Ielasi, Francesco S; Ternifi, Sara; Fontaine, Emeline; Iuso, Domenico; Couté, Yohann; Palencia, Andrés
• Is Part Of: Nucleic acids research. Volume 50:Issue 21(2022)
• Page Start: 12425
• Page End: 12443
• Publication Date: 2022-11-30
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkac878
• Languages: English
• ISSNs: 0305-1048

Abstract

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.