Non-coding RNAs, the cutting edge of histone messages

Abstract

In metazoan the 3′-end processing of histone mRNAs is a conserved process involving the concerted action of many protein factors and the non-coding U7 snRNA. Recently, we identified that the processing of histone pre-mRNAs is promoted by an additional ncRNA, the Y3-derived Y3** RNA. U7 modulates the association of the U7 snRNP whereas Y3** promotes recruitment of CPSF (cleavage and polyadenylation specific factor) proteins to nascent histone transcripts at histone locus bodies (HLBs) in mammals. This enhances the 3′-end cleavage of nascent histone pre-mRNAs and modulates HLB assembly. Here we discuss new insights in the role of ncRNAs in the spatiotemporal control of histone synthesis. We propose that ncRNAs scaffold the formation of functional protein-RNA complexes and their sequential deposition on nascent histone pre-mRNAs at HLBs. These findings add to the multiple roles of ncRNAs in controlling gene expression and may provide new avenues for targeting histone synthesis in cancer.

Functional interactions between scaffold proteins, noncoding RNAs, and genome loci induce liquid‐liquid phase separation as organizing principle for 3‐dimensional nuclear architecture: implications in cancer

“…Nevertheless, many questions still remain about the role of ncRNAs on aberrant nuclear organization in cancer. Interestingly, it has been suggested that ncRNAs serve as scaffolds for the formation of functional protein–RNA complexes and their sequential deposition on histones (105). These aspects are important for understanding how histone synthesis is controlled in tumor cells, which are frequently characterized by an amplification of histone gene loci (106).…”