Pluto Bioinformatics

GSE144323: Dual RNA 3 end processing of H2A.X messenger RNA maintains DNA damage repair throughout the cell cycle

Bulk RNA sequencing

Replication-dependent (RD) histone mRNA are the only non-polyadenylated protein coding transcripts in humans. However, a subset of RD histone genes also expresses polyadenylated mRNA upon terminal differentiation to maintain histone proteins. We now show that even in cycling cells, RD histone genes express some poly(A) mRNA. The H2AFX gene, encoding the DNA damage signalling histone variant H2A.X, expresses both an S-phase-specific SL mRNA ending in the typical stem-loop (SL) structure and substantial amounts of an extended poly(A) mRNA. We show, by the selective removal of either mRNA isoform, that the S-phase-specific H2A.X SL mRNA can generate sufficient histone for deposition onto DNA damage responsive (DDR) chromatin in some cell types. In contrast, when cells have evolved to make predominantly H2A.X poly(A) mRNA they then require de novo H2A.X for efficient DDR. This highlights the importance of differential H2AFX mRNA 3 end processing for the maintenance of effective DDR SOURCE: Esther Griesbach (esther.griesbach@path.ox.ac.uk) - Proudfoot University of Oxford