SUMO Regulates Histone mRNA Processing and Polyadenylation.

Replication-dependent histone genes encode the only non-polyadenylated mRNAs in mammals. Histone pre-mRNAs, which do not contain introns, therefore require only one processing step that involves 3' end recognition and cleavage. Both histone gene expression and pre-mRNA processing take place in specialized nuclear organelles known as histone locus bodies. Recent studies have revealed that polyadenylation of histone mRNAs does occur, however, under specific physiological conditions. These include during normal terminal cellular differentiation, tumorigenesis, and in disease patients with Aicardi-Goutières syndrome. Despite these links between polyadenylation of histone mRNAs, human physiology, and disease, the triggers, the mechanisms, and the consequences of histone mRNA polyadenylation remain poorly defined. In recent studies of small ubiquitin-related modifier (SUMO) knockout cell lines, we have obtained evidence that SUMO1 and SUMO2 play roles in regulating histone pre-mRNA 3' end processing and polyadenylation. This evidence includes alterations in histone locus body size and structure in SUMO1 and SUMO2 knockout cells, as well as mislocalization of key pre-mRNA processing factors required for normal processing. Collectively, our findings provide new insights into control of histone pre-mRNA processing that involves posttranslational protein modifications by SUMO1 and SUMO2.